Tadayoshi Miyamoto

According to prior research, high-intensity endurance training (HIT) conducted more than twice a week significantly improves the maximum oxygen uptake (V_O2max), a marker of cardiorespiratory fitness, compared to low or moderate-intensity training. This training modality not only benefits athletes but also aids individuals with metabolic syndrome and circulatory and respiratory conditions, enhancing their quality of life. Despite these potentials, exploratory studies of exercise regimens with shorter durations, lower frequencies, and fewer sets remain insufficient; thus minimalistic HIT protocols remain under-investigated. In this research, our objective was to investigate the impact of an even less frequent, once-weekly, maximum effort high-intensity training (HIT) on cardiorespiratory function and exercise performance across various age groups. We enrolled 11 healthy participants (4 males and 7 females;age 36.9±16.7 years;height 163.4±11.7cm;weight 58.4±10.6kg) to participate in exhaustive training sessions for 8 weeks. The intensity was set at 80%of their maximum load reached in an initial ramp test (80%WR_max) . Before and after the training, participants underwent ramp test and head-up tilt (orthostatic load) test to assess adaptations in cardiorespiratory function during maximum exercise and circulatory adjustment to postural changes. Exercise performance was evaluated by maximum exercise duration until exhaustion (Exhaustion Time) . Post-training results indicated significant improvements in V_O2max (＋12%, p=0.02), ＋7.5% (p=0.026) WR_max＋12.7%, and Exhaustion Time. Furthermore, in the head-up tilt test, a significant increase in end-tidal CO₂ partial pressure (P_ETCO2) (＋17.5%, p=0.04) was observed in the supine position, and P_ETCO2 increased by ＋11.9% (p=0.03) while tidal volume decreased by -19.9% (p=0.02) in the tilt position. Although no interaction was found in ANOVA, significant Primary effects of training and condition were observed for P_ETCO2. Our findings suggest that once-weekly HIT to maximum exertion enhances cardiorespiratory function and exercise performance. No changes in parameters maintaining blood pressure were observed during the head-up tilt test. These findings may be valuable for future development of efficient exercise training programs for wider age groups.

Although Gaussian white noise (GWN) inputs offer a theoretical framework for identifying higher-order nonlinearity, an actual application to the data of the neural arc of the carotid sinus baroreflex did not succeed in fully predicting the well-known sigmoidal nonlinearity. In the present study, we assumed that the neural arc can be approximated by a cascade of a linear dynamic (LD) component and a nonlinear static (NS) component. We analyzed the data obtained using GWN inputs with a mean of 120 mmHg and standard deviations (SDs) of 10, 20, and 30 mmHg for 15 min each in anesthetized rats (n = 7). We first estimated the linear transfer function from carotid sinus pressure to sympathetic nerve activity (SNA) and then plotted the measured SNA against the linearly predicted SNA. The predicted and measured data pairs exhibited an inverse sigmoidal distribution when grouped into 10 bins based on the size of the linearly predicted SNA. The sigmoidal nonlinearity estimated via the LD-NS model showed a midpoint pressure (104.1 ± 4.4 mmHg for SD of 30 mmHg) lower than that estimated by a conventional stepwise input (135.8 ± 3.9 mmHg, P < 0.001). This suggests that the NS component is more likely to reflect the nonlinearity observed during pulsatile inputs that are physiological to baroreceptors. Furthermore, the LD-NS model yielded higher R2 values compared with the linear model and the previously suggested second-order Uryson model in the testing dataset.NEW & NOTEWORTHY We examined the input-size dependence of the baroreflex neural arc transfer characteristics during Gaussian white noise inputs. A linear dynamic-static nonlinear model yielded higher R2 values compared with a linear model and captured the well-known sigmoidal nonlinearity of the neural arc, indicating that the nonlinear dynamics contributed to determining sympathetic nerve activity. Ignoring such nonlinear dynamics might reduce our ability to explain underlying physiology and significantly limit the interpretation of experimental data.

Background: Alterations in central blood volume (CBV) play a pivotal role in the functionality of the respiratory and circulatory systems. This study elucidates the adaptive changes in respiration, cerebral circulation, and cardiovascular function in response to orthostatic stress in male volleyball players compared to healthy non-athletes. The athletes’ unique physiological adaptability may help them cope with the frequent CBV changes related to their sports activities. Methods: Fourteen male university students participated in this study; seven were volleyball players and seven were non-athletes. Participants underwent a maximal ramp exercise test and a lower body negative pressure (LBNP) test conducted to examine the cardiorespiratory response under LBNP and no-LBNP conditions. Respiratory, metabolic, hemodynamic, and cardiac measurements were collected and analyzed. Results: Volleyball players (Ath group) were significantly taller and exhibited higher maximal oxygen uptake (VO2max) and maximum work rate compared to non-athletes (Non-Ath group). Under the LBNP condition, end-tidal CO2 partial pressure (PETCO2) decreased by 4.1% in the Non-Ath group, but was maintained stable in the Ath group. The CBV reduction rate due to LBNP was notably less in the Ath group (−12.5%) compared to the Non-Ath group (−24.5%). In all participants, a significant correlation was observed between the CBV and PETCO2 reduction rates. However, cerebral blood flow and cardiovascular responses to LBNP load did not differ between the two groups. Conclusion: Male volleyball players demonstrate distinctive adaptability in response to orthostatic stress, specifically in maintaining stable PETCO2 and attenuating CBV reduction rate under LBNP load. These findings suggest that the sport-specific training in volleyball may induce some protective mechanisms against abrupt changes in CBV, although cerebral blood flow and cardiovascular responses appear unaffected. Further research is warranted to understand the underlying mechanisms of these adaptations.

Purpose: High-intensity interval training (HIIT) may induce training-specific physiological adaptations such as improved respiratory and cardiovascular adjustments before and after the onset of high-intensity exercise, leading to improved exercise performance during high-intensity exercise. The present study investigated the effects of HIIT on time-dependent cardiorespiratory adjustment during maximal exercise and before and after initiation of high-intensity exercise, as well as on maximal exercise performance. Methods: 21 healthy male college students were randomly assigned to HIIT group (n = 11) or control group (n = 10). HIIT group performed training on a cycle ergometer once a week for 8 weeks. The training consisted of three bouts of exercise at 95% maximal work rate (WRmax) until exhaustion. Before and after the HIIT program, dynamic cardiorespiratory function was investigated by ramp and step exercise tests, and HIIT-induced cardiac morphological changes were assessed using echocardiography. Results: HIIT significantly improved not only maximal oxygen uptake and minute ventilation, but also maximal heart rate (HR), systolic blood pressure (SBP), and time to exhaustion in both exercise tests (p < 0.05). Time-dependent increases in minute ventilation (VE) and HR before and at the start of exercise were significantly enhanced after HIIT. During high-intensity exercise, there was a strong correlation between percent change (from before to after HIIT program) in time to exhaustion and percent change in HRmax (r = 0.932, p < 0.001). Furthermore, HIIT-induced cardiac morphological changes such as ventricular wall hypertrophy was observed (p < 0.001). Conclusion: We have demonstrated that HIIT at 95% WRmax induces training-specific adaptations such as improved cardiorespiratory adjustments, not only during maximal exercise but also before and after the onset of high-intensity exercise, improvement of exercise performance mainly associated with circulatory systems.

Moxibustion is a traditional East Asian medicine treatment that involves burning moxa directly or indirectly on or near the skin at a specific site of the body, called an acupoint. However, whether moxibustion induces cardiovascular responses by modulating autonomic nervous activity remains unknown. The purpose of this study was to elucidate the effects of indirect moxibustion on cardiovascular responses and autonomic nervous activity. Fifteen healthy volunteers participated in the study. Each subject received regional heat stimulation by indirect moxibustion at the lower leg acupoint. Heart rate, RR intervals, blood pressure and skin temperature were measured continuously for 3 min at rest and 5 min during indirect moxibustion. Local skin temperature increased reaching a peak (45.3 ± 3.3 °C) at 2 min after moxibustion was started, and was accompanied by a significant decrease in heart rate (63.0 ± 7.8 to 60.8 ± 7.8 bpm, p < 0.05) together with a significant increase in root mean square difference of successive RR intervals. Regional heat stimulation by indirect moxibustion induced bradycardic response, which was modulated by autonomic nervous system.

Since the arterial baroreflex system is classified as an immediate control system, the focus has been on analyzing its dynamic characteristics in the frequency range between 0.01 and 1 Hz. Although the dynamic characteristics in the frequency range below 0.01 Hz are not expected to be large, actual experimental data are scant. The aim was to identify the dynamic characteristics of the carotid sinus baroreflex in the frequency range down to 0.001 Hz. The carotid sinus baroreceptor regions were isolated from the systemic circulation, and carotid sinus pressure (CSP) was changed every 10 s according to Gaussian white noise with a mean of 120 mmHg and standard deviation of 20 mmHg for 90 min in anesthetized Wistar-Kyoto rats (n = 8). The dynamic gain of the linear transfer function relating CSP to arterial pressure (AP) at 0.001 Hz tended to be greater than that at 0.01 Hz (1.060 ± 0.197 vs. 0.625 ± 0.067, p = 0.080), suggesting that baroreflex control was largely maintained at 0.001 Hz. Regarding nonlinear analysis, a second-order Uryson model predicted AP with a higher R2 value (0.645 ± 0.053) than a linear model (R2  = 0.543 ± 0.057, p = 0.025) or a second-order Volterra model (R2  = 0.589 ± 0.055, p = 0.045) in testing data. These pieces of information may be used to create baroreflex models that can add a component of autonomic control to a cardiovascular digital twin for predicting acute hemodynamic responses to treatments and tailoring individual treatment strategies.

This study aimed to investigate whether anticipatory cardiorespiratory responses vary depending on the intensity of the subsequent exercise bout, and whether anticipatory cardiorespiratory adjustments contribute importantly to enhancing exercise performance during high-intensity exercise. Eleven healthy men were provided advance notice of the exercise intensity and a countdown to generate anticipation during 10 min prior to exercise at 0, 50, 80 or 95% maximal work-rate (Experiment 1). A different group of subjects (n = 15) performed a time to exhaustion trial with or without anticipatory countdown (Experiment 2). In Experiment 1, heart rate (HR), oxygen uptake (VO2 ) and minute ventilation (VE ) during pre-exercise resting period increased over time and depended on the subsequent exercise intensity. Specifically, there was already a 7.4% increase in HR from more than 5 min prior to the start of exercise at 95% maximal work-rate, followed by progressively augmented increases of 12.5% between 2 and 3 min before exercise, 24.4% between 0 and 1 min before exercise. In Experiment 2, the initial HR for the first 10 s of exercise in the task with anticipation was 11.4% larger compared to without anticipation (p < 0.01), and the difference in HR between the two conditions decreased in a time-dependent manner. In contrast, the initial increases in VO2 and VE were significantly lower in the task with anticipation than that without anticipation. The time to exhaustion during high-intensity exercise was 14.6% longer under anticipation condition compared to no anticipation (135 ± 26 s vs. 119 ± 26 s, p = 0.003). In addition, the enhanced exercise performance correlated positively with increased HR response just before and immediately after exercise onset (p < 0.01). These results showed that anticipatory cardiorespiratory adjustments (feedforward control) via the higher brain that operate before starting exercise may play an important role in minimizing the time delay of circulatory response and enhancing performance after onset of high-intensity exercise in man.

Clonidine is a first-generation central antihypertensive that reduces sympathetic nerve activity (SNA). Although clonidine also exerts peripheral vasoconstriction, the extent to which this vasoconstriction offsets the centrally mediated arterial pressure (AP)-lowering effect remains unknown. In anesthetized rats (n = 8), we examined SNA and AP responses to stepwise changes in carotid sinus pressure under control conditions and after intravenous low-dose (2 μg/kg) and high-dose clonidine (5 μg/kg). In the baroreflex equilibrium diagram analysis, the operating-point AP under the control condition was 115.2 (108.5-127.7) mmHg [median (25th-75th percentile range)]. While the operating-point AP after low-dose clonidine was not significantly different with or without the peripheral effect, the operating-point AP after high-dose clonidine was higher with the peripheral effect than without [81.3 (76.2-98.2) mmHg vs. 70.7 (57.7-96.9), P < 0.05]. The vasoconstrictive effect of clonidine partly offset the centrally mediated AP-lowering effect after high-dose administration.

Muscarinic potassium channels (IK,ACh ) are thought to contribute to the high frequency (HF) dynamic heart rate (HR) response to vagal nerve stimulation (VNS) because they act faster than the pathway mediated by hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. However, the interactions between the two pathways have not yet been fully elucidated. We previously demonstrated that HCN channel blockade by ivabradine (IVA) increased the HF gain ratio of the transfer function from VNS to HR. To test the hypothesis that IVA increases the HF gain ratio via an interaction with IK,ACh , we examined the dynamic HR response to VNS under conditions of control (CNT), IK,ACh blockade by tertiapin-Q (TQ, 50 nM/kg), and TQ plus IVA (2 mg/kg) (TQ + IVA) in anesthetized rats (n = 8). In each condition, the right vagal nerve was stimulated for 10 min with binary white noise signals between 0-10, 0-20, and 0-40 Hz. On multiple regression analysis, the HF gain ratio positively correlated with the VNS rate with a coefficient of 1.691 ± 0.151 (×0.01) (p < 0.001). TQ had a negative effect on the HF gain ratio with a coefficient of -1.170 ± 0.214 (×0.01) (p < 0.001). IVA did not significantly increase the HF gain ratio in the presence of TQ. The HF gain ratio remained low under the TQ + IVA condition compared to controls. These results affirm that the IVA-induced increase in the HF gain ratio is dependent on the untethering of the hyperpolarizing effect of IK,ACh .

BACKGROUND: The purpose of the present study was to investigate the effects of bradycardia induced by pre-exercise acupuncture on heart rate responses during short-duration exercise. METHODS: A total of 29 healthy subjects underwent two protocols: protocol 1 assessed the effects of manual acupuncture on heart rate response during rest, and protocol 2 tested the hypothesis that the bradycardic effects induced by pre-exercise acupuncture continue during low- and high-intensity exercise. Their average age, height, weight, and body mass index were 21.2 ± 2.0 years, 167.2 ± 8.8 cm, 63.8 ± 12.8 kg, and 22.7 ± 3.5 kg/m2, respectively. In acupuncture stimulations for protocols 1 and 2, an acupuncture needle was inserted into the lower leg and manual acupuncture stimulation was performed at 1 Hz. RESULTS: In protocol 1 (resting condition), acupuncture stimulation induced a bradycardic response, which continued for 4 min after the cessation of acupuncture stimulation (p < 0.05). In protocol 2, the bradycardic response induced by pre-exercise acupuncture stimulation remained during low-intensity exercise and in the beginning of high-intensity exercise performed immediately after the cessation of acupuncture stimulation (p < 0.05). However, the effects disappeared when post-acupuncture exercise was performed when the heart rate was approximately 140 beats/min during high-intensity exercise. The rating of perceived exertion after exercise differed significantly between the acupuncture stimulation task (7.9 ± 1.6) and no-stimulation task (8.5 ± 2.0) (p = 0.03) only in the low intensity group. CONCLUSION: This study may provide new insights into the effect of acupuncture stimulation on psycho-physiological conditions during exercise.

NEW FINDINGS: What is the central question of this study? To what extent do hypoxia-induced changes in the peripheral and central respiratory chemoreflex modulate anterior and posterior cerebral oxygen delivery, with corresponding implications for susceptibility to acute mountain sickness? What is the main finding and its importance? We provide evidence for site-specific regulation of cerebral blood flow in hypoxia that preserves oxygen delivery in the posterior but not the anterior cerebral circulation, with minimal contribution from the central respiratory chemoreflex. External carotid artery vasodilatation might prove to be an alternative haemodynamic risk factor that predisposes to acute mountain sickness. ABSTRACT: The aim of the present study was to determine the extent to which hypoxia-induced changes in the peripheral and central respiratory chemoreflex modulate anterior and posterior cerebral blood flow (CBF) and oxygen delivery (CDO2 ), with corresponding implications for the pathophysiology of the neurological syndrome, acute mountain sickness (AMS). Eight healthy men were randomly assigned single blind to 7 h of passive exposure to both normoxia (21% O2 ) and hypoxia (12% O2 ). The peripheral and central respiratory chemoreflex, internal carotid artery, external carotid artery (ECA) and vertebral artery blood flow (duplex ultrasound) and AMS scores (questionnaires) were measured throughout. A reduction in internal carotid artery CDO2 was observed during hypoxia despite a compensatory elevation in perfusion. In contrast, vertebral artery and ECA CDO2 were preserved, and the former was attributable to a more marked increase in perfusion. Hypoxia was associated with progressive activation of the peripheral respiratory chemoreflex (P < 0.001), whereas the central respiratory chemoreflex remained unchanged (P > 0.05). Symptom severity in participants who developed clinical AMS was positively related to ECA blood flow (Lake Louise score, r = 0.546-0.709, P = 0.004-0.043; Environmental Symptoms Questionnaires-Cerebral symptoms score, r = 0.587-0.771, P = 0.001-0.027, n = 4). Collectively, these findings highlight the site-specific regulation of CBF in hypoxia that maintains CDO2 selectively in the posterior but not the anterior cerebral circulation, with minimal contribution from the central respiratory chemoreflex. Furthermore, ECA vasodilatation might represent a hitherto unexplored haemodynamic risk factor implicated in the pathophysiology of AMS.

The arterial baroreflex system plays a key role in maintaining the homeostasis of arterial pressure (AP). Changes in AP affect autonomic nervous activities through the baroreflex neural arc, whereas changes in the autonomic nervous activities, in turn, alter AP through the baroreflex peripheral arc. This closed-loop negative feedback operation makes it difficult to identify open-loop dynamic characteristics of the neural and peripheral arcs. Regarding sympathetic AP controls, we examined the applicability of a nonparametric frequency-domain closed-loop identification method to the carotid sinus baroreflex system in anesthetized rabbits. This article compares the results of an open-loop analysis applied to open-loop data, an open-loop analysis erroneously applied to closed-loop data, and a closed-loop analysis applied to closed-loop data. To facilitate the understanding of the analytical method, sample data files and sample analytical codes were provided. In the closed-loop identification, properties of the unknown central noise that modulated the sympathetic nerve activity and the unknown peripheral noise that fluctuated AP affected the accuracy of the estimation results. A priori knowledge about the open-loop dynamic characteristics of the arterial baroreflex system may be used to advance the assessment of baroreflex function under closed-loop conditions in the future.

Our previous study indicated that intravenously administered ivabradine (IVA) augmented the dynamic heart rate (HR) response to moderate-intensity vagal nerve stimulation (VNS). Considering an accentuated antagonism, the results were somewhat paradoxical; i.e., the accentuated antagonism indicates that an activation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels via the accumulation of intracellular cyclic adenosine monophosphate (cAMP) augments the HR response to VNS, whereas the inhibition of HCN channels by IVA also augmented the HR response to VNS. To remove the possible influence from the accentuated antagonism, we examined the effects of IVA on the dynamic vagal control of HR under β-blockade. In anesthetized rats (n = 7), the right vagal nerve was stimulated for 10 min according to binary white noise signals between 0 and 10 Hz (V0-10), between 0 and 20 Hz (V0-20), and between 0 and 40 Hz (V0-40). The transfer function from VNS to HR was estimated. Under β-blockade (propranolol, 2 mg/kg iv), IVA (2 mg/kg iv) did not augment the asymptotic low-frequency gain but increased the asymptotic high-frequency gain in V0-10 (0.53 ± 0.10 vs. 1.74 ± 0.40 beats/min/Hz, P < 0.01) and V0-20 (0.79 ± 0.14 vs. 2.06 ± 0.47 beats/min/Hz, P < 0.001). These changes, which were observed under a minimal influence from sympathetic background tone, may reflect an increased contribution of the acetylcholine-sensitive potassium channel (IK,ACh) pathway after IVA, because the HR control via the IK,ACh pathway is faster and acts in the frequency range higher than the cAMP-mediated pathway.NEW & NOTEWORTHY Since ivabradine (IVA) inhibits hyperpolarization-activated cyclic nucleotide-gated channels, interactions among the sympathetic effect, vagal effect, and IVA can occur in the control of heart rate (HR). To remove the sympathetic effect, we estimated the transfer function from vagal nerve stimulation to HR under β-blockade in anesthetized rats. IVA augmented the high-frequency dynamic gain during low- and moderate-intensity vagal nerve stimulation. Untethering the hyperpolarizing effect of acetylcholine-sensitive potassium channels after IVA may be a possible underlying mechanism.

This study investigated the effect of low-frequency severe-intensity interval training on the respiratory compensation point (RCP) during incremental exercise test. Eighteen healthy males (age; 20.7 ± 2.2 years, range 18 to 29 years, height; 174.0 ± 5.6 cm, weight; 68.8 ± 13.5 kg) were randomly assigned to an interval training group or a control group. Interval training was conducted once weekly for 3 months. Each session consisted of three bouts of bicycle ergometer exercise at 80% maximum work rate until volitional fatigue. Before (baseline) and after the 3-month intervention, incremental exercise test was performed on a bicycle ergometer for determination of ventilatory threshold (VT), RCP, and peak oxygen consumption (V̇O2 peak). The training program resulted in significant increases of V̇O2 peak (+ 14%, p < 0.001, η p 2 = 0.437), oxygen consumption (V̇O2) at VT (+ 18%, p < 0.001, η p 2 = 0.749) and RCP (+ 15%, p = 0.03, η p 2 = 0.239) during incremental exercise test in the training group. Furthermore, a significant positive correlation was observed between the increase in V̇O2 peak and increase in V̇O2 at RCP after intervention (r = 0.87, p = 0.002) in the training group. Tidal volumes at VT (p = 0.04, η p 2 = 0.270) and RCP (p = 0.01, η p 2 = 0.370) also increased significantly after intervention compared to baseline. Low-frequency severe-intensity interval training induced a shift in RCP toward higher work rate accompanied by higher tidal volume during incremental exercise test.

NEW FINDINGS: What is the central question of this study? What are the dynamic characteristics of cerebrovascular carbon dioxide reactivity and the central respiratory chemoreflex? What is the main finding and its importance? The transfer function gain from the end-tidal partial pressure of carbon dioxide to cerebral blood flow or ventilation decreased in the high frequency range at rest and during exercise. These findings indicate that the dynamic characteristics of both systems were not constant in all frequency ranges, and this trend was not modified by exercise. ABSTRACT: The purpose of this study was to examine the dynamic characteristics of cerebrovascular reactivity and ventilatory response to change in arterial CO2 in all frequency ranges at rest using frequency domain analysis, and also to examine whether this is modified by dynamic exercise as with the traditionally determined cerebrovascular CO2 reactivity. In nine healthy young subjects, at rest and during exercise (cycling exercise at constant predetermined work rate corresponding to a V ̇ O 2 level of 0.90 l min-1 ), the dynamic characteristics of cerebrovascular CO2 reactivity and the central respiratory chemoreflex were assessed by transfer function analysis using a binary white-noise sequence (0-7% inspired CO2 fraction) from the end-tidal partial pressure of CO2 ( P ETC O 2 ) to the mean middle cerebral artery mean blood velocity (MCA Vm ) or minute ventilation ( V ̇ E ), respectively. In the high frequency range, both transfer function gains decreased but, interestingly, the cut-off frequency in the transfer function gain from P ETC O 2 to MCA Vm response was higher than that from P ETC O 2 to V ̇ E response at rest (0.024 vs. 0.015 Hz) and during exercise (0.030 vs. 0.011 Hz), indicating that cerebrovascular CO2 reactivity or central respiratory chemoreflex was not constant in all frequency ranges, and this trend was not modified by exercise. These findings suggest that dynamic characteristics of the cerebrovascular CO2 reactivity or central chemoreflex need to be assessed to identify the whole system because the traditional method cannot identify the property of time response of these systems.

Background: High intensity interval training (HIT) is more effective than continuous training in enhancing cardio-respiratory function and symptom severity in chronic heart failure (CHF). We examined how HIT affects ventilatory regulation. Methods: In 7 healthy subjects, at rest and during exercise at light and heavy intensities, we separately characterized respiratory controller and plant (subsystems) of chemoreflex by changing inspiratory CO2 fraction and by making subjects alter ventilation (VE), respectively. Results: HIT did not affect both subsystems at rest and during light intensity exercise. During heavy intensity exercise, rightward shift of central controller characteristics mainly attributed to lower VE (-9.4%, p<0.01) and higher end tidal PCO2 (+4.4%, p<0.05) after HIT. Conclusion: Weekly high intensity interval training attenuates the respiratory drive during heavy exercise through desensitization of the respiratory central controller. Such mechanism may contribute to favorable effects of HIT in CHF.

Fragrance inhalation of essential oils is widely used in aromatherapy, and it is known to affect blood pressure (BP) and heart rate (HR) via autonomic control of circulation. In this study, we aimed to test the hypothesis that the changes in hemodynamics with fragrance inhalation were observed along with changes in muscle sympathetic nerve activity (MSNA). In study 1, thirteen healthy men were exposed to fragrance stimulation of grapefruit essential oil for 10 min, and BP, HR, and MSNA were continuously measured. In study 2, another nine healthy men were exposed to the same fragrance stimulation; responses in BP and HR were continuously measured, and plasma noradrenaline and cortisol concentrations were determined. We found that diastolic BP increased significantly during fragrance inhalation, while the other variables remained unchanged in both studies. Although MSNA burst frequency, burst incidence, and total activity remained unchanged during fragrance inhalation, we found a significant linear correlation between changes in diastolic BP in the last 5 min of fragrance inhalation and changes in MSNA burst frequency. The plasma cortisol concentration decreased significantly at 10 min of fragrance inhalation, though the noradrenaline concentration remained unchanged. These results suggest, for the first time, that changes in BP with fragrance inhalation of essential oil are associated with changes in MSNA even with decreased stress hormone.

The cardiovascular effects of the autonomic nervous system (ANS) are modulated by inputs from peripheral sensors and other brain regions. However, it currently remains unknown whether the manual acupuncture (MA) stimulation of different acupuncture points evokes different responses by the heart and vasculature, a phenomenon known as "site specificity". Sixty healthy subjects were randomly divided into a control group and MA stimulation groups at the lower leg, ear, abdomen, and forearm. MA was performed at 1 Hz for 2 min. A depressor response was observed only in the lower leg stimulation group, in which mean blood pressure significantly decreased from 83.4 ± 10.1 to 80.9 ± 11.7 mmHg (p < 0.003). A bradycardic response was elicited in all MA stimulation groups. There was no significant differences in the magnitude of the bradycardic response between groups. MA-induced cardiovascular responses, which may be mediated by the modulation of ANS, differ depending on acupuncture points.

NEW FINDINGS: What is the central question of this study? There is an interaction between the regulatory systems of respiration and cerebral blood flow, because the mediator (CO2 ) is the same for both physiological systems. We examined whether the traditional method for determining cerebrovascular reactivity to CO2 is modified by changes in respiration. What is the main finding and its importance? Cerebrovascular reactivity was modified by voluntary changes in respiration during hypercapnia. This finding suggests that an alteration in the respiratory system may result in under- or overestimation of cerebrovascular reactivity determined by traditional methods in healthy adults. ABSTRACT: The cerebral vasculature is sensitive to changes in the arterial partial pressure of CO2 . This physiological mechanism has been well established as a cerebrovascular reactivity to CO2 (CVR). However, arterial CO2 may not be an independent variable in the traditional method for assessment of CVR, because the cerebral blood flow response is also affected by the activation of respiratory drive or higher centres in the brain. We hypothesized that CVR is modified by changes in respiration. To test our hypothesis, in the present study, 10 young, healthy subjects performed hyper- or hypoventilation to change end-tidal CO2 ( P ET , C O 2 ) with different concentrations of CO2 in the inhaled gas (0, 2.0 and 3.5%). We measured middle cerebral artery mean blood flow velocity by transcranial Doppler ultrasonography to identify the cerebral blood flow response to change in P ET , C O 2 during each set of conditions. In each set of conditions, P ET , C O 2 was significantly altered by changes in ventilation, and middle cerebral artery mean blood flow velocity changed accordingly. However, the relationship between changes in middle cerebral artery mean blood flow velocity and P ET , C O 2 as a response curve of CVR was reset upwards and downwards by hypo- and hyperventilation, respectively, compared with CVR during normal ventilation. The findings of the present study suggest the possibility that an alteration in respiration might lead to under- or overestimation of CVR determined by the traditional methods.

Complex interactions are known to occur between the sympathetic and parasympathetic controls of the heart. Although sympathetic nerve stimulation (SNS) usually augments the heart rate (HR) response to vagal nerve stimulation (VNS), exogenously administered norepinephrine (NE) can attenuate the HR response as well as the myocardial interstitial acetylcholine (ACh) release during VNS. To provide a basis for an integrative knowledge about the opposing adrenergic effects on the vagal control of the heart, we examined whether SNS significantly attenuates VNS-induced myocardial interstitial ACh release in the in vivo beating heart. In nine anesthetized rats, changes in HR and myocardial interstitial ACh release in response to 5- and 20-Hz VNS were examined in both the absence and presence of a 5-Hz background SNS. The SNS significantly enhanced the VNS-induced HR reduction during 20-Hz VNS (-101.2 ± 33.1 vs. -163.0 ± 34.9 beats/min, P < 0.001, a 60% augmentation). By contrast, the SNS significantly attenuated the ACh release during 20-Hz VNS (4.30 ± 0.72 vs. 3.80 ± 0.75 nM, P < 0.01, a 12% attenuation). In conclusion, SNS exerted only a moderate inhibitory effect on the VNS-induced myocardial interstitial ACh release in the in vivo beating heart.

Although daily variations of blood pressure (BP) predict cardiovascular event risk, their assessment requires ambulatory BP monitoring which hinders the clinical application of this approach. Since the baroreflex is a major determinant of BP variations, especially in the frequency range of 0.01-0.1 Hz (baro-frequency), we hypothesized that the power spectral density (PSD) of short-term BP recordings in the baro-frequency range may predict daily variations of BP. In nine-week-old Wister-Kyoto male rats (N =5) with or without baroreflex dysfunction, we telemetrically recorded continuous BP for 24 hours and estimated PSD using Welch's periodogram for the recordings during the 12-hour light period. We compared the reference PSD of 12-hour recording with the PSDs obtained from shorter data lengths ranging from 5 to 240 minutes. The 30-minute BP recordings reproduced PSD of 12-hour recordingswell, and PSD in the baro-frequency range paralleled the standard deviation of 12-hour BP. Thus, the PSD of 30-minute BP reflects the daily BP variability in rats. In human subjects, we estimated PSD from 30-minute noninvasive continuous BP recordings. The rat and human PSDs shared remarkably similar characteristics. Furthermore, comparison of PSD between elderly and young subjects suggested that the baro-frequency range in humans overlapped with that in rats. In conclusion, PSD derived from 30-minute BP recordings is capable of predicting daily BP variations. Our proposed method may serve as a simple, noninvasive and practical tool for predicting cardiovascular events in the clinical setting.

Changes in cerebral blood flow (CBF) subsequent to alterations in the partial pressures of oxygen and carbon dioxide can modify dynamic cerebral autoregulation (CA). While cognitive activity increases CBF, the extent to which it impacts CA remains to be established. In the present study we determined whether dynamic CA would decrease during a cognitive task and whether hypoxia would further compound impairment. Fourteen young healthy subjects performed a simple Go/No-go task during normoxia and hypoxia (inspired O₂ fraction = 12%), and the corresponding relationship between mean arterial pressure (MAP) and mean middle cerebral artery blood velocity (MCA V_mean) was examined. Dynamic CA and steady-state changes in MCA V in relation to changes in arterial pressure were evaluated with transfer function analysis. While MCA V_mean increased during the cognitive activity ( P &lt; 0.001), hypoxia did not cause any additional changes ( P = 0.804 vs. normoxia). Cognitive performance was also unaffected by hypoxia (reaction time, P = 0.712; error, P = 0.653). A decrease in the very low- and low-frequency phase shift (VLF and LF; P = 0.021 and P = 0.01) and an increase in LF gain were observed ( P = 0.037) during cognitive activity, implying impaired dynamic CA. While hypoxia also increased VLF gain ( P &lt; 0.001), it failed to cause any additional modifications in dynamic CA. Collectively, our findings suggest that dynamic CA is impaired during cognitive activity independent of altered systemic O₂ availability, although we acknowledge the interpretive complications associated with additional competing, albeit undefined, inputs that could potentially distort the MAP-MCA V_mean relationship. NEW &amp; NOTEWORTHY During normoxia, cognitive activity while increasing cerebral perfusion was shown to attenuate dynamic cerebral autoregulation (CA) yet failed to alter reaction time, thereby questioning its functional significance. No further changes were observed during hypoxia, suggesting that impaired dynamic CA occurs independently of altered systemic O₂ availability. However, impaired dynamic CA may reflect a technical artifact, given the confounding influence of additional inputs that could potentially distort the mean arterial pressure-mean middle cerebral artery blood velocity relationship.

New Findings: What is the central question of this study? The lack of useful small-animal models for studying exercise hyperpnoea makes it difficult to investigate the underlying mechanisms of exercise-induced ventilatory abnormalities in various disease states. What is the main finding and its importance? We developed an anaesthetized-rat model for studying exercise hyperpnoea, using a respiratory equilibrium diagram for quantitative characterization of the respiratory chemoreflex feedback system. This experimental model will provide an opportunity to clarify the major determinant mechanisms of exercise hyperpnoea, and will be useful for understanding the mechanisms responsible for abnormal ventilatory responses to exercise in disease models. Abstract: Exercise-induced ventilatory abnormalities in various disease states seem to arise from pathological changes of respiratory regulation. Although experimental studies in small animals are essential to investigate the pathophysiological basis of various disease models, the lack of an integrated framework for quantitatively characterizing respiratory regulation during exercise prevents us from resolving these problems. The purpose of this study was to develop an anaesthetized-rat model for studying exercise hyperpnoea for quantitative characterization of the respiratory chemoreflex feedback system. In 24 anaesthetized rats, we induced muscle contraction by stimulating bilateral distal sciatic nerves at low and high voltage to mimic exercise. We recorded breath-by-breath respiratory gas analysis data and cardiorespiratory responses while running two protocols to characterize the controller and plant of the respiratory chemoreflex. The controller was characterized by determining the linear relationship between end-tidal CO2 pressure ((Formula presented.)) and minute ventilation ((Formula presented.)), and the plant by the hyperbolic relationship between (Formula presented.) and (Formula presented.). During exercise, the controller curve shifted upward without change in controller gain, accompanying increased oxygen uptake. The hyperbolic plant curve shifted rightward and downward depending on exercise intensity as predicted by increased metabolism. Exercise intensity-dependent changes in operating points ((Formula presented.) and (Formula presented.)) were estimated by integrating the controller and plant curves in a respiratory equilibrium diagram. In conclusion, we developed an anaesthetized-rat model for studying exercise hyperpnoea, using systems analysis for quantitative characterization of the respiratory system. This novel experimental model will be useful for understanding the mechanisms responsible for abnormal ventilatory responses to exercise in disease models.

Aims: To assess the acute effects of intravenous ivabradine, a selective bradycardic agent, on carotid sinus baroreflex-mediated sympathetic arterial pressure (AP) and heart rate (HR) responses. Methods and results: In anesthetized and vagotomized Wistar–Kyoto rats (n = 6), carotid sinus baroreceptor regions were isolated. Changes in splanchnic sympathetic nerve activity (SNA), AP, and HR in response to a step-wise pressure input were examined before and after intravenous ivabradine (2 mg/kg). Ivabradine did not affect the response range of SNA (91.8 ± 6.5 vs. 93.5 ± 9.8%) or AP (89.6 ± 10.6 vs. 91.0 ± 9.7 mm Hg). Ivabradine significantly reduced the minimum HR from 369.4 ± 8.4 to 223.3 ± 13.2 (P &lt 0.001) but did not attenuate the HR response range (69.1 ± 7.0 vs. 82.5 ± 9.6 beats/min). Conclusions: Ivabradine does not acutely affect baroreflex-mediated sympathetic AP regulation and also spares the magnitude of the sympathetic HR response, despite significant bradycardia. The preserved sympathetic HR response, which could not be afforded by beta-blockers, may contribute to some beneficial clinical effects of ivabradine.

Previously, we demonstrated that pre-exercise feed-forward cardiorespiratory control mechanism by the higher brain center plays a significant role in enhancing physiological efficiency to exercise. If such mechanism of central predictive and prospective control plays an important role in optimization of respiratory and circulatory control during exercise, the quantitative and temporal dynamics of cardiorespiratory response before exercise may depend on subsequent exercise intensity. To confirm this hypothesis, we investigated the predictive control of respiratory and circulatory systems before onset of exercise at low-, moderate-and high-work intensities. Eight healthy males underwent a 10 min seated rest period which followed by an ergometer bicycle exercise for 2 min. The gas-exchange parameters were recorded by breath-by-breath method. During pre-exercise resting period, minute ventilation and heart rate and were augmented immediately 1 minute before the higher intensity exercise(P<0.05). This intensity-dependent preparatory cardiorespiratory responses can be caused by central neural control mechanisms involving learning and memory.

The effects of water exercise on gut hormone concentrations and appetite currently remain unclear. The aim of the present study was to investigate the effects of treadmill walking in water on gut hormone concentrations and appetite. Thirteen men (mean ± s.d. age: 21.6 ± 2.2 years, body mass index: 22.7 ± 2.8 kg/m2, peak oxygen uptake (VO2peak): 49.8 ± 7.8 mL/kg per min) participated in the walking in water and on land challenge. During the study period, ratings of subjective feelings of hunger, fullness, satiety and motivation to eat were reported on a 100-mm visual analog scale. A test meal was presented after walking, and energy intake (EI) was calculated. Blood samples were obtained during both trials to measure glucagon-like peptide-1 (GLP-1), peptide YY (PYY) and acylated ghrelin (AG) concentrations. Hunger scores (How hungry do you feel?) were significantly lower during the water trial than during the land trial (P &lt 0.05). No significant differences were observed in EI between water and land trials. GLP-1 concentrations were significantly higher in the water trial than in the land trial (P &lt 0.05). No significant differences were observed in PYY concentrations between water and land trials. AG concentrations were significantly lower in the water trial than in the land trial (P &lt 0.01). In conclusion, changes in gut hormone concentrations during walking in water contribute to the exercise-induced suppression of appetite and provide novel information on the influence of walking in water on the acute regulation of appetite.

AIMS: Moxonidine is a centrally acting antihypertensive agent with a selectivity to I1-imidazoline receptors higher than that to α2-adrenergic receptors. The present study aimed to quantify a peripheral effect of moxonidine on carotid sinus baroreflex-mediated sympathetic arterial pressure (AP) regulation separately from its central effect. MAIN METHODS: In eight anesthetized Wistar rats, changes in efferent sympathetic nerve activity (SNA) and AP in response to a carotid sinus pressure input were compared before and during an intravenous administration of moxonidine (100μgkg-1 bolus followed by a continuous infusion at 200μg·kg-1·h-1). KEY FINDINGS: Moxonidine significantly narrowed the range of the AP response (55.3±5.8 to 39.1±6.1mmHg, P<0.05) without changing the minimum AP (77.2±6.4 to 80.7±5.1mmHg, not significant). In the neural arc, moxonidine reduced the minimum SNA (56.6±5.9 to 29.7±6.2%, P<0.05) without affecting the range of the SNA response (45.3±5.5 to 40.2±5.0%, not significant). In the peripheral arc, moxonidine increased the intercept (3.0±8.5 to 51.1±7.2mmHg, P<0.01) and reduced the slope (1.28±0.06 to 0.92±0.15mmHg/%, P<0.05). SIGNIFICANCE: Moxonidine increased AP at any given SNA, suggesting that the peripheral vasoconstrictive effect is stronger than generally recognized. The peripheral vasoconstrictive effect of moxonidine may partly offset the vasodilatory effect attained by centrally-mediated sympathoinhibition.

Although hypoxia has the potential to impair the cognitive function, the effects of acute hypoxia on the high-order brain function (executive and/or inhibitory processing) and somatosensory ascending processing remain unknown. We tested the hypothesis that acute hypoxia impairs both motor executive and inhibitory processing and somatosensory ascending processing. Fifteen healthy subjects performed two sessions (sessions 1 and 2), consisting of electroencephalographic event-related potentials with somatosensory Go/No-go paradigms and somatosensory-evoked potentials (SEPs) under two conditions (hypoxia and normoxia) on different days. On 1 day, participants breathed room air in the first and second sessions of the experiment; on the other day, participants breathed room air in the first session, and 12% O-2 in the second session. Acute hypoxia reduced the peak amplitudes of Go-P300 and No-go-P300, and delayed the peak latency of Go-P300. However, no significant differences were observed in the peak amplitude or latency of N140, behavioral data, or the amplitudes and latencies of individual SEP components between the two conditions. These results suggest that acute hypoxia impaired neural activity in motor executive and inhibitory processing, and delayed higher cognitive processing for motor execution, whereas neural activity in somatosensory processing was not affected by acute hypoxia. NEW & NOTEWORTHY Hypoxia has the potential to impair the cognitive function, but the effects of acute hypoxia on the cognitive function remain debatable. We investigated the effects of acute hypoxia on human cognitive processing using electroencephalographic event-related potentials and somatosensory-evoked potentials. Acute normobaric hypoxia impaired neural activity in motor executive and inhibitory processing, but no significant differences were observed in neural activity in somatosensory processing.

Although the pulsatility of an input pressure is an important factor that determines the arterial baroreflex responses, whether the difference in the input waveforms can meaningfully affect the baroreflex function remains unknown. This study aimed to compare baroreflex responses between two distinct pressure waveforms: a forward saw wave (FSW) and a backward saw wave (BSW). In seven anesthetized rats, carotid sinus pressure was exposed to the FSW or the BSW with a mean of 120 mmHg, pulse pressure of 40 mmHg, and pulse frequency of 1 Hz. Changes in efferent sympathetic nerve activity (SNA) and arterial pressure (AP) during six consecutive saw wave trials (FSW1, BSW1, FSW2, BSW2, FSW3, and BSW3) were examined. The steady-state SNA value during FSW1 was 91.1 +/- 1.9%, which was unchanged during FSW2 and FSW3 but significantly increased during BSW1 (106.6 +/- 3.4%, P &lt; 0.01), BSW2 (110.6 +/- 2.5%, P &lt; 0.01), and BSW3 (111.6 +/- 2.3%, P &lt; 0.01). The steady-state AP value during FSW1 was 98.2 +/- 8.1 mmHg, which was unchanged during FSW2 and FSW3 but significantly increased during BSW1 (106.7 +/- 7.4 mmHg, P &lt; 0.01), BSW2 (105.6 +/- 7.8 mmHg, P &lt; 0.01), and BSW3 (103.8 +/- 7.2 mmHg, P &lt; 0.05). In conclusion, the FSW was more effective than the BSW in reducing mean SNA and AP. The finding could be applied to designing an artificial pulsatile pressure such as that generated by left ventricular assist devices. NEW & NOTEWORTHY This study examined whether the waveforms of an input pressure alone can affect the baroreflex function by using a forward saw wave and a backward saw wave with the same mean pressure, pulse pressure, and pulse frequency. The forward saw wave was more effective than the backward saw wave in reducing sympathetic nerve activity and arterial pressure. The finding could be applied to designing an artificial pulsatile pressure such as that generated by left ventricular assist devices.

Central chemoreflex activation induces sympatho-excitation. However, how central chemoreflex interacts with baroreflex function remains unknown. This study aimed to examine the impact of central chemoreflex on the dynamic as well as static baroreflex functions under open-loop conditions. In 15 anesthetized, vagotomized Sprague-Dawley rats, we isolated bilateral carotid sinuses and controlled intra-sinus pressure (CSP). We then recorded sympathetic nerve activity (SNA) at the celiac ganglia, and activated central chemoreflex by a gas mixture containing various concentrations of CO2. Under the baroreflex open-loop condition (CSP = 100 mmHg), central chemoreflex activation linearly increased SNA and arterial pressure (AP). To examine the static baroreflex function, we increased CSP stepwise from 60 to 170 mmHg and measured steady-state SNA responses to CSP (mechanoneural arc), and AP responses to SNA (neuromechanical arc). Central chemoreflex activation by inhaling 3% CO2 significantly increased SNA irrespective of CSP, indicating resetting of the mechanoneural arc, but did not change the neuromechanical arc. As a result, central chemoreflex activation did not change baroreflex maximum total loop gain significantly (-1.29 ± 0.27 vs. -1.68 ± 0.74, N.S.). To examine the dynamic baroreflex function, we randomly perturbed CSP and estimated transfer functions from 0.01 to 1.0 Hz. The transfer function of the mechanoneural arc approximated a high-pass filter, while those of the neuromechanical arc and total (CSP-AP relationship) arcs approximated a low-pass filter. In conclusion, central chemoreflex activation did not alter the transfer function of the mechanoneural, neuromechanical, or total arcs. Central chemoreflex modifies hemodynamics via sympathoexcitation without compromising dynamic or static baroreflex AP buffering function.

We aimed to develop a novel method to quantitatively evaluate the effects of odor stimulation on cardiorespiratory functions over time, and to examine the potential usefulness of clinical aromatherapy. Eighteen subjects participated. Nine people were assigned to each of the two resting protocols. Protocol 1: After resting for 2 min in a sitting position breathing room air, the subject inhaled either air or air containing sweet marjoram essential oil from the Douglas bag for 6 min, Protocol 2: After resting for 5 min in a supine position, the subject inhaled the essential oil for 10 min, and then recovered for 10 min breathing room air. All subjects inhaled the essential oil through a face mask attached to one-way valve, and beat-to-beat heart rate (HR) and arterial blood pressure (BP) as well as breath-by-breath respiratory variables were continuously recorded. In both protocols, during fragrance inhalation of the essential oil, time-dependent decrease in mean BP and HR were observed (P<0.05). During post-inhalation recovery, the significant fragrance-induced bradycardic effect lasted at least 5 min (- 3.1 ± 3.9% vs. pre-inhalation baseline value, p<0.05). The mean BP response at the start of odor stimulation was approximated by a first-order exponential model. However, such fragrance-induced changes were not observed in the respiratory variables. We established a novel approach to quantitatively and accurately evaluate the effects of quantitative odor stimulation on dynamic cardiorespiratory functions, and the duration of the effect. This methodological approach may be useful for scientific evaluation of aromatherapy as an approach to integrated medicine, and the mechanisms of action of physiological effects in fragrance compounds.

The respiratory control system is an important chemoreflex-feedback control system that maintains arterial partial pressures of CO₂ (P_aCO2), O₂ and pH remarkably constant via ventilatory regulation. It can be divided into two subsystems: a controller (controlling element) and a plant (controlled element). The respiratory operating point (ventilatory or P_aCO2 response) is determined by the interplay between the controller (arterial P_CO2 [P_aCO2] → minute ventilation [V_E] relation) and plant (V_E → P_aCO2 relation) subsystem elements within the respiratory control system. This review outlines the methodology of converting the closed loop of the respiratory control system to an open loop state, then simplifying the controller and plant subsystems, and identifying the input−output relationship using a systems physiological technique (equilibrium diagram method). Changes in central hemodynamics, exercise stimulus, and regular exercise training modify V_E and/or P_aCO2 levels at rest and during exercise. These respiratory changes can be quantitatively explained by changes in two subsystem elements on the respiratory equilibrium diagram. Using this analysis technique that allows an integrated and quantitative description of the whole respiratory control system will greatly advance the elucidation of pathological conditions manifesting breathing disorders and respiratory regulation during exercise. By repeating thought experiments utilizing this kind of mathematic model and physiological experiments that provide evidence, deeper understanding will be achieved concerning prediction of the behavior of biological systems beyond the physiological range and understanding of the pathophysiology of diseases that are difficult to study by clinical research.

PURPOSE: Acupuncture stimulation is known to act on the autonomic nervous system and elicits depressor and bradycardic effects. However, previous studies on humans did not conduct quantitative analyses on optimal acupuncture conditions such as the stimulation frequency and duration to achieve maximum depressor and bradycardic effects. The aim of the present study was to investigate the effects of varying stimulation frequencies of electroacupuncture on time-dependent changes in blood pressure and heart rate in humans. METHODS: Twelve healthy volunteers participated in the study. An acupuncture needle was inserted at the Ximen acupoint (PC4 according to WHO nomenclature), located at the anterior aspect of the forearm. An electrical stimulation was delivered through the acupuncture needle at an intensity of 1 V, pulse width of 5 ms, and stimulation frequencies of 0.5, 1, 5, and 10 Hz in a random order. The duration of electroacupuncture was 6 min, during which blood pressure and heart rate responses were monitored. RESULTS: Group-averaged data indicated that 1-Hz electroacupuncture decreased blood pressure and heart rate. Blood pressure was significantly decreased from the prestimulation baseline value of 86.6 ± 2.9 to 81.4 ± 2.3 mmHg during 4-6 min of 1-Hz electroacupuncture (mean ± SE, P < 0.01). Heart rate was also significantly decreased (from 66.2 ± 2.0 to 62.7 ± 1.7 beats/min, P < 0.01). CONCLUSIONS: These results provide fundamental evidence that bradycardiac and depressor responses are effectively produced by electrical acupuncture in humans.

<jats:p> The purpose of the present study was to examine whether the response of cerebral blood flow to an acute change in perfusion pressure is modified by an acute increase in central blood volume. Nine young, healthy subjects voluntarily participated in this study. To measure dynamic cerebral autoregulation during normocapnic and hypercapnic (5%) conditions, the change in middle cerebral artery mean blood flow velocity was analyzed during acute hypotension caused by two methods: 1) thigh-cuff occlusion release (without change in central blood volume); and 2) during the recovery phase immediately following release of lower body negative pressure (LBNP; −50 mmHg) that initiated an acute increase in central blood volume. In the thigh-cuff occlusion release protocol, as expected, hypercapnia decreased the rate of regulation, as an index of dynamic cerebral autoregulation (0.236 ± 0.018 and 0.167 ± 0.025 s<jats:sup>−1</jats:sup>, P = 0.024). Compared with the cuff-occlusion release, the acute increase in central blood volume (relative to the LBNP condition) with LBNP release attenuated dynamic cerebral autoregulation ( P = 0.009). Therefore, the hypercapnia-induced attenuation of dynamic cerebral autoregulation was not observed in the LBNP release protocol ( P = 0.574). These findings suggest that an acute change in systemic blood distribution modifies dynamic cerebral autoregulation during acute hypotension. </jats:p>