Slow respiratory stimulant effect of hyperoxia in chemodenervated decerebrate cats.

A direct stimulating action of oxygen on the CO2 respiratory control system was determined from steady-state and dynamic observations in unanesthetized decerebrate cats. In peripheral nerve-intact animals, inhalation of oxygen (1 atm) produced a small but significant shift to the left as well as a decrease in slope in the steady-state VT vs. log PACO2 relationship. Carotid sinus neurotomy more than doubled the shift, to the extent that the mean PACO2 apneic point was lowered by 6.5 mmHg. Neither vagotomy nor chronic ablation of the area postrema had any detectable influence on the stimulating effect of oxygen on CO2 responsiveness. The arterial-alveolar PCO2 difference, prior to and following carotid chemo-denervation, remained unchanged or was increased by a negligible amount during oxygen inhalation. The oxygen threshold for respiratory stimulation, obtained isocapnically, occurred between 115 and 200 mmHg; VT then increased exponentially tending to level off as PAO2 approached 1 atm. The dynamic response to sudden presentation of oxygen after carotid chemodenervation consisted of a monotonic rise in VT, starting after 20-30 s with a t 1/2 of about 75 s.     

Chemical and mechanical determinants of apnea during high-frequency ventilation

The factors responsible for the apnea observed during high-frequency ventilation (HFV) were evaluated in 14 pentobarbital sodium-anesthetized cats. A multiple logistic regression analysis provided an estimate of the probability of apnea during HFV as a function of four respiratory variables: mean airway pressure (Paw), tidal volume (VT), frequency, and arterial PCO2 (PaCO2). When mean Paw was 2 cmH2O, PaCO2, VT, and their interaction contributed significantly to the probability of apnea during HFV. At a low value of PaCO2 (25 Torr), the probability of apnea had a minimum value of 0.19 and gradually increased toward 1.0 as VT increased from 0.5 to 7 ml/kg. At higher levels of PaCO2 (30 and 35 Torr) the probability of apnea was zero in the low range of VT but sharply approached 1.0 above a VT of approximately 2.0 ml/kg. However, when Paw was increased to 6 cmH2O, only PaCO2 was an important determinant of apnea. In this case, the probability of apnea was 0.51 when PaCO2 was 25 Torr but decreased to 0.22 when PaCO2 was raised to 25 Torr. At neither Paw was the probability of apnea dependent on frequency. These results suggest that chemoreceptor inputs, in addition to both static and dynamic lung mechanoreceptor afferents, are responsible for determining the output of the central respiratory centers during HFV.     

Baroreceptor influence on a spinal cardiovascular reflex

A stretch of the walls of the thoracic aorta, performed in vagotomized cats without obstructing aortic flow, induces increases in heart rate, myocardial contractility, and arterial pressure. These reflex responses are still present after high spinal section. Cats under chloralose-urethane anesthesia were vagotomized and one carotid sinus was isolated and perfused with arterial blood at constant flow. The contralateral carotid sinus nerve and both aortic nerves were sectioned. A stretch of the walls of the thoracic aorta between the 7th and 10th intercostal arteries induced a reflex increase in mean arterial pressure 29 +/- 2 mmHg (mean +/- SE). Stepwise increases of carotid sinus pressure (CSP) or electrical stimulation of the carotid sinus nerve induced stepwise decreases of this reflex response. At maximal baroreceptor stimulation (CSP 212 +/- 9 mmHg) the reflex response to aortic stretch was reduced by 42%. These experiments show that this spinal cardiovascular reflex is at least partially under the inhibitory control of the baroreceptor input.     

Glutamate release in midbrain periaqueductal gray by activation of skeletal muscle receptors and arterial baroreceptors

We have previously reported that both skeletal muscle receptor and arterial baroreceptor afferent inputs activate neurons in the dorsolateral (DL) and lateral regions of the midbrain periaqueductal gray (PAG). In this study, we determined whether the excitatory amino acid glutamate (Glu) is released to mediate the increased activity in these regions. Static contraction of the triceps surae muscle for 4 min was evoked by electrical stimulation of the L7 and S1 ventral roots in cats. Activation of arterial baroreceptor was induced by intravenous injection of phenylephrine. The endogenous release of Glu from the PAG was recovered with the use of a microdialysis probe. Glu concentration was measured by the HPLC method. Muscle contraction increased mean arterial pressure (MAP) from 98 +/- 10 to 149 +/- 12 mmHg (P < 0.05) and increased Glu release in the DL and lateral regions of the middle PAG from 0.39 +/- 0.10 to 0.73 +/- 0.12 microM (87%, P < 0.05) in intact cats. After sinoaortic denervation and vagotomy were performed, contraction increased MAP from 95 +/- 12 to 158 +/- 15 mmHg, and Glu from 0.34 +/- 0.08 to 0.54 +/- 0.10 microM (59%, P < 0.05). The increases in arterial pressure and Glu were abolished by muscle paralysis. Phenylephrine increased MAP from 100 +/- 13 to 162 +/- 22 mmHg and increased Glu from 0.36 +/- 0.10 to 0.59 +/- 0.18 microM (64%, P < 0.05) in intact animals. Denervation abolished this Glu increase. Summation of the changes in Glu evoked by muscle receptor and arterial baroreceptor afferent inputs was greater than the increase in Glu produced when both reflexes were activated simultaneously in intact state (123% vs. 87%). These data demonstrate that activation of skeletal muscle receptors evokes release of Glu in the DL and lateral regions of the middle PAG, and convergence of afferent inputs from muscle receptors and arterial baroreceptors in these regions inhibits the release of Glu. These results suggest that the PAG is a neural integrating site for the interaction between the exercise pressor reflex and the arterial baroreceptor reflex.     

Estimates of mean alveolar PCO2 during steady-state exercise in man: a theoretical study.

The partial pressure of carbon dioxide in arterial blood is an important operator in the control of breathing, by actions on peripheral and central chemoreceptors. In experiments on man we must often assume that lung alveolar PCO2 equals arterial PCO2 and obtain estimates of the former derived from measurements in expired gas sampled at the mouth. This paper explores the potential errors of such estimates, which are magnified during exercise. We used a published model of the cardiopulmonary system to simulate various levels of exercise up to 300 W. We tested three methods of estimating mean alveolar PCO2 (PACO2) against the true value derived from a time average of the within-breath oscillation in steady-state exercise. We used both sinusoidal and square-wave ventilatory flow wave forms. Over the range 33-133 W end-tidal PCO2 (P(et)CO2) overestimated PACO2 progressively with increasing workload, by about 4 mmHg at 133 W with normal respiratory rate for that load. PCO2 by a graphical approximation technique (PgCO2; "graphical method") underestimated PACO2 by 1-2 mmHg. PCO2 from an experimentally obtained empirical equation (PnjCO2; "empirical method") overestimated PACO2 by 0.5-1.0 mmHg. Graphical and empirical methods were insensitive to alterations in cardiac output or respiratory rate. End-tidal PCO2 was markedly affected by respiratory rate during exercise, the overestimate of PACO2 increasing if respiratory rate was slowed. An increase in anatomical dead space with exercise tends to decrease the error in P(et)CO2 and increase the error in the graphical method. Changes in the proportion of each breath taken up by inspiration make no important difference, and changes in functional residual capacity, while important in principle, are too small to have any major effect on the estimates. Changes in overall alveolar ventilation which alter steady-state PACO2 over a range of 30-50 mmHg have no important effect. At heavy work loads (200-300 W), P(et)CO2 grossly overestimates by 6-9 mmHg. The graphical method progressively underestimates, by about 5 mmHg at 300 W. A simulated CO2 response (the relation between ventilation and increasing PCO2) performed at 100 W suggests that a response slope close to the true one can be obtained by using any of the three methods. The graphical method gave results closest to the true absolute values. Either graphical or empirical methods should be satisfactory for detecting experimentally produced changes in PACO2 during steady-state exercise, to make comparisons between different steady-state exercise loads, and to assess CO2 response in exercise.(ABSTRACT TRUNCATED AT 400 WORDS)     

刺激肾神经传入纤维的降压反应与颈动脉窦压力感受性反射的相互作用

在麻醉兔,研究了刺激肾神经传入纤维与颈动脉窦压力感受性反射在减压反射中的相互作用。电刺激肾神经传入纤维引起平均动脉压(MAP)下降,下降程度在一定范围有赖于刺激频率。当颈动脉窦被隔离和主动脉神经切断后,随着颈动脉窦内压逐渐升高,刺激肾神经传入纤维引起的减压反应不断减弱。在45至135mmHg 之间的7个颈动脉窦内压(ISP)水平,刺激肾神经传入纤维,并画出刺激前和刺激时的 ISP-MAP 关系曲线。在颈动脉窦内压为75至105mmHg 之间,刺激肾神经传入纤维显著降低 ISP-MAP 关系曲线的斜率和对ISP 的平均动脉压反应范围。这些结果提示:(1)颈动脉窦压力感受器的传入冲动可调制刺激肾神经传入纤维的降压反应,在一定范围内与颈动脉窦内压呈反比;(2)刺激肾神经传入纤维明显减弱颈动脉窦的压力感受性反射。     

Blood pressure regulation in the three-toed sloth, Bradypus variegatus

The aim of this study was to elucidate the role of the baroreflex in blood pressure control in sloths, Bradypus variegatus, since these animals show labile levels in this parameter. Unanesthetized cannulated sloths were positioned in an experimental chair and the arterial catheter was coupled to a strain gauge pressure transducer. Blood pressure was monitored before, during and after the administration of phenylephrine (0.0625 to 4 microg/kg) and sodium nitroprusside (0.0625 to 2 microg/kg), bringing about changes in mean blood pressure from +/-30 mmHg in relation to control values. The relation between heart rate changes due to blood pressure variation was estimated by linear regression analysis. The slope was considered the reflex baroreceptor gain. The results (means+/-SD) showed that the reflex baroreceptor gain was -0.3+/-0.1 bpm/mmHg (r=0.88) to phenylephrine and -0.5+/-0.1 bpm/mmHg (r=0.92) to sodium nitroprusside, denoting a reduced reflex baroreceptor gain when compared with other mammals, suggesting that in sloths the baroreceptors are minimally involved in the buffering reflex response to these drugs. These findings suggest that the labile blood pressure could be influenced or be a result of this lowering in the reflex baroreceptor gain.     

Effect of SO2 on control of breathing in anesthetized cats

In seven anesthetized tracheotomized cats we studied the acute respiratory effects of SO2 inhalation at different steady-state levels of arterial CO2 tension (Paco2). During room air breathing, SO2 (0.05%) addition caused a progressive reduction in tidal volume (VT) and increases in both respiratory frequency (f) and pulmonary resistance (RL). Atropine sulfate abolished the bronchoconstriction response to SO2 and thus permitted the study of the influence of SO2 on VT and f in the absence of constricted airways. Despite marked reductions in the VT VS. PaCO2 relationships with SO2 exposure after atropine, the relationship between pulmonary ventilation (VE) and PaCO2 was not signifcantly altered. This was the case since SO2 caused solely a reduction in inspiratory duration (Ti), affecting neither the mean rate of rise of inspiratory activity (i.e., VT/Ti) nor the relationship between Ti and breath duration. Thus, airways irritation with SO2 produced rapid, shallow breathing characterized by a shortening of inspiratory and total respiratory cycle times with no change in the rate of development of inspiratory activity. The findings suggest an influence exclusively concerned with the timing of inspiration. Perhaps premature onset of inspiratory activity accounts for the observed effects.     

Medullary lateral tegmental field mediates the cardiovascular but not respiratory component of the Bezold-Jarisch reflex in the cat

We determined the effects of bilateral microinjection of muscimol and excitatory amino acid receptor antagonists into the medullary lateral tegmental field (LTF) on changes in sympathetic nerve discharge (SND), mean arterial pressure (MAP), and phrenic nerve activity (PNA; artificially ventilated cats) or intratracheal pressure (spontaneously breathing cats) elicited by right atrial administration of phenylbiguanide (PBG; i.e., the Bezold-Jarisch reflex) in dial-urethane anesthetized cats. The PBG-induced depressor response (-66 +/- 8 mmHg; mean +/- SE) was converted to a pressor response after muscimol microinjection in two of three spontaneously breathing cats and was markedly reduced in the other cat; however, the duration of apnea (20 +/- 3 vs. 17 +/- 7 s) was essentially unchanged. In seven paralyzed, artificially ventilated cats, muscimol microinjection significantly (P < 0.05) attenuated the PBG-induced fall in MAP (-39 +/- 7 vs. -4 +/- 4 mmHg) and the magnitude (-98 +/- 1 vs. -35 +/- 13%) and duration (15 +/- 2 vs. 3 +/- 2 s) of the sympathoinhibitory response. In contrast, the PBG-induced inhibition of PNA was unaffected (3 cats). Similar results were obtained by microinjection of an N-methyl-D-aspartate (NMDA) receptor antagonist, D(-)-2-amino-5-phosphonopentanoic acid, into the LTF. In contrast, neither the cardiovascular nor respiratory responses to PBG were altered by blockade of non-NMDA receptors with 1,2,3,4-tetrahydro-6-nitro-2,3-dioxobenzo[f]quinoxaline-7-sulfonamide. We conclude that the LTF subserves a critical role in mediating the sympathetic and cardiovascular components of the Bezold-Jarisch reflex. Moreover, these data show separation of the pathways mediating the respiratory and cardiovascular responses of this reflex at a level central to bulbospinal outflows to phrenic motoneurons and preganglionic sympathetic neurons.     

Hypoxemia alone does not explain blood pressure elevations after obstructive apneas

In patients with obstructive sleep apnea (OSA), substantial elevations of systemic blood pressure (BP) and depressions of oxyhemoglobin saturation (SaO2) accompany apnea termination. The causes of the BP elevations, which contribute significantly to nocturnal hypertension in OSA, have not been defined precisely. To assess the relative contribution of arterial hypoxemia, we observed mean arterial pressure (MAP) changes following obstructive apneas in 11 OSA patients during non-rapid-eye-movement (NREM) sleep and then under three experimental conditions: 1) apnea with O2 supplementation; 2) hypoxemia (SaO2 80%) without apnea; and 3) arousal from sleep with neither hypoxemia nor apnea. We found that apneas recorded during O2 supplementation (SaO2 nadir 93.6% +/- 2.4; mean +/- SD) in six subjects were associated with equivalent postapneic MAP elevations compared with unsupplemented apneas (SaO2 nadir 79-82%): 18.8 +/- 7.1 vs. 21.3 +/- 9.2 mmHg (mean change MAP +/- SD); in the absence of respiratory and sleep disruption in eight subjects, hypoxemia was not associated with the BP elevations observed following apneas: -5.4 +/- 19 vs. 19.1 +/- 7.8 mmHg (P less than 0.01); and in five subjects, auditory arousal alone was associated with MAP elevation similar to that observed following apneas: 24.0 +/- 8.1 vs. 22.0 +/- 6.9 mmHg. We conclude that in NREM sleep postapneic BP elevations are not primarily attributable to arterial hypoxemia. Other factors associated with apnea termination, including arousal from sleep, reinflation of the lungs, and changes of intrathoracic pressure, may be responsible for these elevations.     

Mechanisms of blood pressure regulation that differ in men repeatedly exposed to high-G acceleration

The purpose of this study was to test the hypothesis that repeated exposure to high acceleration (G) would be associated with enhanced functions of specific mechanisms of blood pressure regulation. We measured heart rate (HR), stroke volume (SV), cardiac output (), mean arterial blood pressure, central venous pressure, forearm and leg vascular resistance, catecholamines, and changes in leg volume (%DeltaLV) during various protocols of lower body negative pressure (LBNP), carotid stimulation, and infusions of adrenoreceptor agonists in 10 males after three training sessions on different days over a period of 5-7 days using a human centrifuge (G trained). These responses were compared with the same measurements in 10 males who were matched for height, weight, and fitness but did not undergo G training (controls). Compared with the control group, G-trained subjects demonstrated greater R-R interval response to equal carotid baroreceptor stimulation (7.3 +/- 1.2 vs. 3.9 +/- 0.4 ms/mmHg, P = 0.02), less vasoconstriction to equal low-pressure baroreceptor stimulation (-1.4 +/- 0.2 vs. -2.6 +/- 0.3 U/mmHg, P = 0.01), and higher HR (-1.2 +/- 0.2 vs. -0.5 +/- 0.1 beats. min(-1). mmHg(-1), P = 0.01) and alpha-adrenoreceptor response (32.8 +/- 3.4 vs. 19.5 +/- 4.7 U/mmHg, P = 0.04) to equal dose of phenylephrine. During graded LBNP, G-trained subjects had less decline in and SV, %DeltaLV, and elevation in thoracic impedance. G-trained subjects also had greater total blood (6,497 +/- 496 vs. 5,438 +/- 228 ml, P = 0.07) and erythrocyte (3,110 +/- 364 vs. 2,310 +/- 96 ml, P = 0.06) volumes. These results support the hypothesis that exposure to repeated high G is associated with increased capacities of mechanisms that underlie blood pressure regulation.     

Cardiovascular and respiratory responses to slow ramp carotid sinus pressures in the dog

The respiratory and mean arterial pressure (MAP) responses to slow ramp pressure stimulation of carotid baroreceptors were compared in pentobarbital-anesthetized vagotomized dogs breathing 100% O2. Carotid sinus pressure (CSP) was raised from 50 (control) to 220 mmHg and then returned to control as linear ramps (+/- 1 mmHg/s) in isolated sinuses. MAP, heart rate (HR), ventilation (VE), frequency (f), and tidal volume (VT) were expressed as percent of control. The maximum difference between responses to positive and negative ramps at a given CSP (MAX) and the average difference (AVG) served as indicators of the hysteresis for each response. In 27 dogs MAP changed monotonically with varying CSP with insignificant (P = 0.27, MAX) or barely significant (P = 0.03, AVG) hysteresis, monotonic function being one that is continuously nondecreasing or continuously nonincreasing. Similar responses were obtained for HR. VE decreased as CSP increased, but the change was not monotonic. During negative ramp, VE increased back to control with an overshoot. Hysteresis for VE was pronounced (P less than 0.0001, both measures). The VE response was primarily determined by f; VT increased with CSP. To eliminate secondary respiratory effects due to alterations in MAP, in seven dogs similar experiments were performed after ganglionic blockade with hexamethonium. Hysteresis in VE and f persisted. To assess the role of changing arterial PCO2 (PaCO2) on VE, the CSP was held constant (after a ramp rise) at 140, 150, or 180 mmHg before reducing it at -1 mmHg/s to 50 mmHg; however, a significant hysteresis in VE was still observed. Further experiments, to eliminate secondary reflexes due to altered PaCO2, were performed in seven dogs after ganglionic blockade and paralysis with Flaxedil, with phrenic nerve activity as an indicator of ("neural") respiration. The hysteresis in VE and f were no longer significant. In summary, the results indicate that 1) slow ramp carotid baroreceptor stimulation elicits both VE and cardiovascular responses, the VE response showing a dramatically higher hysteresis than the cardiovascular responses; 2) the ventilatory hysteresis is partially explained by the secondary changes in PaCO2 and perhaps by cardiovascular variables; and 3) the central processing of the baroventilatory reflex appears to be rate sensitive at a slower rate of pressure change than that which causes rate sensitivity in the baropressure reflex.     

Central integration of muscle reflex and arterial baroreflex in midbrain periaqueductal gray: roles of GABA and NO

It has been suggested that the midbrain periaqueductal gray (PAG) is a neural integrating site for the interaction between the muscle pressor reflex and the arterial baroreceptor reflex. The underlying mechanisms are poorly understood. The purpose of this study was to examine the roles of GABA and nitric oxide (NO) in modulating the PAG integration of both reflexes. To activate muscle afferents, static contraction of the triceps surae muscle was evoked by electrical stimulation of the L7 and S1 ventral roots of 18 anesthetized cats. In the first group of experiments (n = 6), the pressor response to muscle contraction was attenuated by bilateral microinjection of muscimol (a GABA receptor agonist) into the lateral PAG [change in mean arterial pressure (DeltaMAP) = 24 +/- 5 vs. 46 +/- 8 mmHg in control]. Conversely, the pressor response was significantly augmented by 0.1 mM bicuculline, a GABAA receptor antagonist (DeltaMAP = 65 +/- 10 mmHg). In addition, the effect of GABAA receptor blockade on the reflex response was significantly blunted after sinoaortic denervation and vagotomy (n = 4). In the second group of experiments (n = 8), the pressor response to contraction was significantly attenuated by microinjection of L-arginine into the lateral PAG (DeltaMAP = 26 +/- 4 mmHg after L-arginine injection vs. 45 +/- 7 mmHg in control). The effect of NO attenuation was antagonized by bicuculline and was reduced after denervation. These data demonstrate that GABA and NO within the PAG modulate the pressor response to muscle contraction and that NO attenuation of the muscle pressor reflex is mediated via arterial baroreflex-engaged GABA increase. The results suggest that the PAG plays an important role in modulating cardiovascular responses when muscle afferents are activated.     

Effects of almitrine on hypoglossal and phrenic electroneurograms

Almitrine increases breathing by stimulating peripheral chemoreceptors. Previous studies suggest clinical usefulness in the adult with chronic obstructive pulmonary disease, but little data are available to decide whether almitrine would be helpful in diseases involving pharyngeal airway obstruction, such as apnea of prematurity or obstructive sleep apnea. We investigated the effect of intravenous almitrine on hypoglossal (HG), an upper airway nerve, and phrenic (PHR) neural activity in eight alpha-chloralose-urethan anesthetized, paralyzed, vagotomized, and artificially ventilated cats. Recordings were made of raw and integrated HG and PHR electroneurograms (ENGs), alveolar PCO2, arterial PO2, arterial blood pressure, and rectal temperature. A dose-response study of cumulative almitrine doses ranging from 0.1 to 4.0 mg/kg was performed in three cats. The interactive effects of almitrine and hypoxic stimulation were investigated in four cats. The interactive effects of almitrine and hypercapnic stimulation were investigated in five cats. The interactive effects of almitrine and ventilatory timing were investigated in six cats. We found that 1) almitrine doses as low as 0.1 mg/kg iv increased both HG and PHR ENG activity, with a maximum effect at approximately 1.0 mg/kg; 2) almitrine markedly increased HG and PHR ENG activity at all arterial PO2 values from 35-175 Torr; 3) almitrine increased HG and PHR ENG activity at all arterial PCO2 values from 30-70 Torr; and 4) almitrine increased the ratio of tidal volume to inspiratory time and decreased the inspiratory muscle duty cycle at normoxia and eucapnia.     

Effects of lower body negative pressure on cardiac and vascular responses to carotid baroreflex stimulation

The aim of this study was to assess carotid baroreflex responses during graded lower body negative pressure (LBNP). In 12 healthy subjects (age 29+/-4 years) we applied sinusoidal neck suction (0 to -30 mmHg) at 0.1 Hz to examine the sympathetic modulation of the heart and blood vessels and at 0.2 Hz to assess the effect of parasympathetic stimulation on the heart. Responses to neck suction were determined as the change in spectral power of RR-interval and blood pressure from baseline values. Measurements were carried out during progressive applications (0 to -50 mmHg) of LBNP. Responses to 0.1 and 0.2 Hz carotid baroreceptor stimulations during low levels of LBNP (-10 mmHg) were not significantly different from those measured during baseline. At higher levels of LBNP, blood pressure responses to 0.1 Hz neck suction were significantly enhanced, but with no significant change in the RR-interval response. LBNP at all levels had no effect on the RR-interval response to 0.2 Hz neck suction. The unchanged responses of RR-interval and blood pressure to neck suction during low level LBNP at -10 mmHg suggest no effect of cardiopulmonary receptor unloading on the carotid arterial baroreflex, since this LBNP level is considered to stimulate cardiopulmonary but not arterial baroreflexes. Enhanced blood pressure responses to neck suction during higher levels of LBNP are not necessarily the result of a reflex interaction but may serve to protect the circulation from fluctuations in blood pressure while standing.     

Analysis of afferent,central, and efferent components of the baroreceptor reflex in mice

Studies of genetically modified mice provide a powerful approach to investigate consequences of altered gene expression in physiological and pathological states. The goal of the present study was to characterize afferent, central, and efferent components of the baroreceptor reflex in anesthetized Webster 4 mice. Baroreflex and baroreceptor afferent functions were characterized by measuring changes in renal sympathetic nerve activity (RSNA) and aortic depressor nerve activity (ADNA) in response to nitroprusside- and phenylephrine-induced changes in arterial pressure. The data were fit to a sigmoidal logistic function curve. Baroreflex diastolic pressure threshold (P(th)), the pressure at 50% inhibition of RSNA (P(mid)), and baroreflex gain (maximum slope) averaged 74 +/- 5 mmHg, 101 +/- 3 mmHg, and 2.30 +/- 0.54%/mmHg, respectively (n = 6). The P(th), P(mid), and gain for the diastolic pressure-ADNA relation (baroreceptor afferents) were similar to that observed for the overall reflex averaging 79 +/- 9 mmHg, 101 +/- 4 mmHg, and 2.92 +/- 0.53%/mmHg, respectively (n = 5). The central nervous system mediation of the baroreflex and the chronotropic responsiveness of the heart to vagal efferent activity were independently assessed by recording responses to electrical stimulation of the left ADN and the peripheral end of the right vagus nerve, respectively. Both ADN and vagal efferent stimulation induced frequency-dependent decreases in heart rate and arterial pressure. The heart rate response to ADN stimulation was nearly abolished in mice anesthetized with pentobarbital sodium (n = 4) compared with mice anesthetized with ketamine-acepromazine (n = 4), whereas the response to vagal efferent stimulation was equivalent under both types of anesthesia. Application of these techniques to studies of genetically manipulated mice can be used to identify molecular mechanisms of baroreflex function and to localize altered function to afferent, central, or efferent sites.     

Central volume expansion is pivotal for sustained decrease in heart rate during seated to supine posture change

During prolonged, static carotid baroreceptor stimulation by neck suction (NS) in seated humans, heart rate (HR) decreases acutely and thereafter gradually increases. This increase has been explained by carotid baroreceptor adaptation and/or buffering by aortic reflexes. During a posture change from seated to supine (Sup) with similar carotid stimulation, however, the decrease in HR is sustained. To investigate whether this discrepancy is caused by changes in central blood volume, we compared (n = 10 subjects) the effects of 10 min of seated NS (adjusted to simulate carotid stimulation of a posture change), a posture change from seated to Sup, and the same posture change with left atrial (LA) diameter maintained unchanged by lower body negative pressure (Sup + LBNP). During Sup, the prompt decreases in HR and mean arterial pressure (MAP) were sustained. HR decreased similarly within 30 s of NS (65 +/- 2 to 59 +/- 2 beats/min) and Sup + LBNP (65 +/- 2 to 58 +/- 2 beats/min) and thereafter gradually increased to values of seated. MAP decreased similarly within 5 min during Sup + LBNP and NS (by 7 +/- 1 to 9 +/- 1 mmHg) and thereafter tended to increase toward values of seated subjects. Arterial pulse pressure was increased the most by Sup, less so by Sup + LBNP, and was unchanged by NS. LA diameter was only increased by Sup. In conclusion, static carotid baroreceptor stimulation per se causes the acute (<30 s) decrease in HR during a posture change from seated to Sup, whereas the central volume expansion (increased LA diameter and/or arterial pulse pressure) is pivotal to sustain this decrease. Thus the effects of central volume expansion override adaptation of the carotid baroreceptors and/or buffering of aortic reflexes.     

Cardiovascular changes during underwater static and dynamic breath-hold dives in trained divers

Limited information exists concerning arterial blood pressure (BP) changes in underwater breath-hold diving. Simulated chamber dives to 50 m of freshwater (mfw) reported very high levels of invasive BP in two divers during static apnea (SA), whereas a recent study using a noninvasive subaquatic sphygmomanometer reported unchanged or mildly increased values at 10 m SA dive. In this study we investigated underwater BP changes during not only SA but, for the first time, dynamic apnea (DA) and shortened (SHT) DA in 16 trained breath-hold divers. Measurements included BP (subaquatic sphygmomanometer), ECG, and pulse oxymetry (arterial oxygen saturation, SpO?, and heart rate). BP was measured during dry conditions, at surface fully immersed (SA), and at 2 mfw (DA and SHT DA), whereas ECG and pulse oxymetry were measured continuously. We have found significantly higher mean arterial pressure (MAP) values in SA (～40%) vs. SHT DA (～30%). Postapneic recovery of BP was slightly slower after SHT DA. Significantly higher BP gain (mmHg/duration of apnea in s) was found in SHT DA vs. SA. Furthermore, DA attempts resulted in faster desaturation vs. SA. In conclusion, we have found moderate increases in BP during SA, DA, and SHT DA. These cardiovascular changes during immersed SA and DA are in agreement with those reported for dry SA and DA.     

Independent modification of baroreceptor and exercise pressor reflex function by nitric oxide in nucleus tractus solitarius

It has been suggested that nitric oxide (NO) is a key modulator of both baroreceptor and exercise pressor reflex afferent signals processed within the nucleus tractus solitarius (NTS). However, studies investigating the independent effects of NO within the NTS on the function of each reflex have produced inconsistent results. To address these concerns, the effects of microdialyzing 10 mM L-arginine, an NO precursor, and 20 mM N(G)-nitro-L-arginine methyl ester (L-NAME), an NO synthase inhibitor, into the NTS on baroreceptor and exercise pressor reflex function were examined in 17 anesthetized cats. Arterial baroreflex regulation of heart rate was quantified using vasoactive drugs to induce acute changes in mean arterial pressure (MAP). To activate the exercise pressor reflex, static hindlimb contractions were induced by electrical stimulation of spinal ventral roots. To isolate the exercise pressor reflex, contractions were repeated after barodenervation. The gain coefficient of the arterial cardiac baroreflex was significantly different from control (-0.24 +/- 0.04 beats.min(-1).mmHg(-1)) after the dialysis of L-arginine (-0.18 +/- 0.02 beats.min(-1).mmHg(-1)) and L-NAME (-0.29 +/- 0.02 beats.min(-1).mmHg(-1)). In barodenervated animals, the peak MAP response to activation of the exercise pressor reflex (change in MAP from baseline, 39 +/- 7 mmHg) was significantly attenuated by the dialysis of L-arginine (change in MAP from baseline, 29 +/- 6 mmHg). The results demonstrate that NO within the NTS can independently modulate both the arterial cardiac baroreflex and the exercise pressor reflex. Collectively, these findings provide a neuroanatomical and chemical basis for the regulation of baroreflex and exercise pressor reflex function within the central nervous system.     

Cardiovascular effects of static carotid baroreceptor stimulation during water immersion in humans

We hypothesized that the more-pronounced hypotensive and bradycardic effects of an antiorthostatic posture change from seated to supine than water immersion are caused by hydrostatic carotid baroreceptor stimulation. Ten seated healthy males underwent five interventions of 15-min each of 1) posture change to supine, 2) seated water immersion to the Xiphoid process (WI), 3) seated neck suction (NS), 4) WI with simultaneous neck suction (-22 mmHg) adjusted to simulate the carotid hydrostatic pressure increase during supine (WI + NS), and 5) seated control. Left atrial diameter increased similarly during supine, WI + NS, and WI and was unchanged during control and NS. Mean arterial pressure (MAP) decreased the most during supine (7 +/- 1 mmHg, P < 0.05) and less during WI + NS (4 +/- 1 mmHg) and NS (3 +/- 1 mmHg). The decrease in heart rate (HR) by 13 +/- 1 beats/min (P < 0.05) and the increase in arterial pulse pressure (PP) by 17 +/- 4 mmHg (P < 0.05) during supine was more pronounced (P < 0.05) than during WI + NS (10 +/- 2 beats/min and 7 +/- 2 mmHg, respectively) and WI (8 +/- 2 beats/min and 6 +/- 1 mmHg, respectively, P < 0.05). Plasma vasopressin decreased only during supine and WI, and plasma norepinephrine, in addition, decreased during WI + NS (P < 0.05). In conclusion, WI + NS is not sufficient to decrease MAP and HR to a similar extent as a 15-min seated to supine posture change. We suggest that not only static carotid baroreceptor stimulation but also the increase in PP combined with low-pressure receptor stimulation is a possible mechanism for the more-pronounced decrease in MAP and HR during the posture change.