Effects of hydralazine on renal sympathetic nerve activity in normal and congestive heart failure rats

We investigated the effects of hydralazine on renal sympathetic nerve activity in anaesthetized heart failure rats. Sham-operated rats (group 1) received 0.5 mg kg^?1 of hydralazine as bolus and were then infused with 0.3–0.5 mg kg^?1 h^?1 for 3 h intravenously. Heart failure rats received either the same regime (group 2) as group 1, or the same volume of vehicle (group 3). Heart failure rats exhibited lower mean blood pressure (P < 0.05) and elevated renal sympathetic nerve activity (P < 0.01) in the basal state. In group 2, the mean blood pressure decreased 26% after 30 min of hydralazine administration and remained lower for 3 h, with unchanged renal sympathetic nerve activity. In group 1, the mean blood pressure decreased 36%, and the heart rate and renal sympathetic nerve activity were significantly inhibited. Bilateral vagotomy did not alter renal sympathetic nerve response to hydralazine, but resulted in tachycardia. The results indicate that hydralazine, despite its profound hypotensive effect, did not activate renal sympathetic nerve activity in heart failure rats and inhibited renal sympathetic nerve activity in sham-operated rats. This inhibition was not mediated through the vagal nerve.     

Power spectral analysis of heart rate and blood pressure variability in anaesthetized dogs.

Short-term oscillation of heart rate and blood pressure are mainly regulated by the automatic nervous system. It has been proposed that non-neural factors, such as changes in intrathoracic pressure, can strongly modulate this rhythmicity. Our aim was to evaluate the effect of changing intrathoracic pressure and central autonomic nervous activity on heart rate and blood pressure variability. Evaluation was performed by using spectral analysis techniques with autoregressive modelling. The variability in heart rate and blood pressure remained in animals with open chest or paralysed respiratory muscles. After vagotomy, the variability in heart rate decreased, but not that of blood pressure. Total spinal anaesthesia elicited a decrease in the variability in blood pressure. The pharmacological blockade of alpha- and beta-receptors further decreased both variabilities. It was concluded that in anaesthetized dogs heart rate and blood pressure variability are mainly of central origin and non-neural factors have only minor effect on these central rhythms. High (> 0.15 Hz), medium (0.07-0.15 Hz) and, obviously low (0.00-0.07 Hz) frequency variations in heart rate are mostly mediated vagally. In blood pressure, medium and obviously low frequency variations are modulated by sympathetic nervous system, whereas high frequency variations are secondary to the heart rate variation.     

Changes in renal sympathetic outflow during hypotensive haemorrhage in rats

The goal of this study was to investigate changes in renal sympathetic outflow during hypotensive haemorrhage. Normotensive Wistar-Kyoto rats were anaesthetized with chloralose (50 mg kg-1) and bled to an arterial blood pressure of 50 mmHg for 30 min. Changes in heart rate (HR) and renal nerve activity (RNA) were registered. The hypotensive haemorrhage induced a short-lasting sympathetic excitation that was followed within 5-10 min by a powerful sympathetic inhibition and bradycardia. The average maximal decrease in sympathetic activity was 65% and the maximal decrease in heart rate was 45 beats min-1. There was a close correlation between changes in heart rate and renal sympathetic activity. The marked depressor response was due at least in part to activation of vagal afferents because the depressor responses were acutely reversed by bilateral cervical vagotomy. As cardiac afferents are known to be activated by prostaglandins and bradykinins, and these agents are released by myocardial ischaemia, haemorrhage was repeated after use of indomethacin and aprotinin (a protein inhibitor decreasing bradykinin formation), and a marked sympathetic inhibition could still be elicited upon haemorrhage. We therefore suggest that the likely mechanism for activation of the vagal afferents is a squeezing of the myocardium when the heart has to contract around an almost empty chamber. In conclusion, this study demonstrated that hypotensive haemorrhage triggers profound inhibition of RNA in rats and that this sympathoinhibition is mediated primarily by mechanically sensitive cardiac vagal afferents.     

Effects of diazepam on the carotid sinus baroreflex control of circulation in rabbits

To examine the effects of diazepam on the carotid sinus baroreflex control of circulation, bilateral carotid occlusion was performed on 14 conscious rabbits with aortic denervation. The responses of mean arterial pressure, heart rate, cardiac output and total peripheral resistance were obtained. The haemodynamic responses to carotid occlusion were evaluated at cumulative doses of 0.5 and 1.0 mg kg-1 of diazepam. The administration of diazepam decreased cardiac output and increased total peripheral resistance significantly, but did not affect the arterial pressure and heart rate. The response of total peripheral resistance to carotid occlusion was significantly increased from 0.118 +/- 0.018 (mean +/- SE) to 0.154 +/- 0.026 mmHg min ml-1 at 1.0 mg kg-1 of diazepam. The heart rate response was attenuated significantly from 41 +/- 5 to 24 +/- 4 beats min-1 at 1.0 mg kg-1 of diazepam. Diazepam did not alter the response of arterial pressure to carotid occlusion. We suggest that the dissociated effects of diazepam on the reflex control of circulation reflect the dissociated influences of diazepam on the central sympathetic and vagal-mediated pathways.     

Circulatory depression following low frequency stimulation of the sciatic nerve in anesthetized rats

Earlier-experiments have shown that afferent-electrical-stimulation-of-the sciatic nerve for 30 min induces a long-lasting post-stimulatory endorphin-dependent decrease in blood pressure in awake spontaneously hypertensive rats (SHR). In the present study we have examined whether this depressor response can be observed also in anesthetized SHR. The sciatic nerve was stimulated for 30 min with low-frequent (3 Hz) trains of impulses and the changes in blood pressure, heart rate and renal nerve activity were observed during the stimulation and in the post-stimulatory period. Animals anesthetized with Nembutal, Althesin and N₂O did not show any post-stimulatory depression. In contrast, during chloralose anesthesia combined with muscle paralysis with Flaxedil, sciatic nerve stimulation induced a long-lasting post-stimulatory decrease in blood pressure due to central inhibition of sympathetic activity. The decrease in blood pressure could be prevented by naloxone and was therefore likely to be mediated via activation of central endorphin systems.     

Noise-enhanced heart rate and sympathetic nerve responses to oscillatory lower body negative pressure in humans

By injecting noise into the carotid sinus baroreceptors, we previously showed that heart rate (HR) responses to weak oscillatory tilt were enhanced via a mechanism known as "stochastic resonance." It remains unclear, however, whether the same responses would be observed when using oscillatory lower body negative pressure (LBNP), which would unload the cardiopulmonary baroreceptors with physically negligible effects on the arterial system. Also, the vasomotor sympathetic activity directly controlling peripheral resistance against hypotensive stimuli was not observed. We therefore investigated the effects of weak (0 to approximately -10 mmHg) oscillatory (0.03 Hz) LBNP on HR and muscle sympathetic nerve activity (MSNA) while adding incremental noise to the carotid sinus baroreceptors via a pneumatic neck chamber. The signal-to-noise ratio of HR, cardiac interbeat interval, and total MSNA were all significantly improved by increasing noise intensity, while there was no significant change in the arterial blood pressure in synchronized with the oscillatory LBNP. We conclude that the stochastic resonance, affecting both HR and MSNA, results from the interaction of noise with the signal in the brain stem, where the neuronal inputs from the arterial and cardiopulmonary baroreceptors first come together in the nucleus tractus solitarius. Also, these results indicate that the noise could induce functional improvement in human blood pressure regulatory system in overcoming given hypotensive stimuli.     

Effect of gastric distension on cardiovascular parameters: gastrovascular reflex is attenuated in the elderly

Stretching the stomach wall in young healthy subjects causes an increase in muscle sympathetic nerve activity and in blood pressure, the gastrovascular reflex. We compared healthy elderly subjects with healthy young subjects to find out whether the gastrovascular reflex attenuates in normal ageing and we studied whether there was a difference in autonomic function or gastric compliance that could explain this possible attenuation. Muscle sympathetic nerve activity, finger blood pressure and heart rate were continuously recorded during stepwise isobaric gastric distension using a barostat in eight healthy young (6 men and 2 women, 27 ± 3.2 years, mean ± s.e.m. ) and eight healthy elderly subjects (7 men and 1 woman, 76 ± 1.5 years). Changes in cardiac output and total peripheral arterial resistance were calculated from the blood pressure signal. The baseline mean arterial pressure and muscle sympathetic nerve activity were higher in the elderly group (both P < 0.05) and muscle sympathetic nerve activity increase during the cold pressor test was lower in the elderly group ( P = 0.005). During stepwise gastric distension, the elderly subjects showed an attenuated increase in muscle sympathetic nerve activity compared to the young subjects ( P < 0.01). The older group tended to show a higher increase in mean arterial pressure ( P = 0.08), heart rate ( P = 0.06) and total peripheral arterial resistance ( P = 0.09) The cardiac output rose slightly in both groups without significant difference between groups. The fundic compliance did not differ between groups. We conclude that stepwise gastric distension caused an increase in muscle sympathetic nerve activity in both groups, but the increase in the elderly was attenuated.     

Central blood volume influences sympathetic sudomotor nerve traffic in warm humans

The objective of this study was to test whether changes in central blood volume can induce reflex effects on sweating. Multi-unit skin sympathetic nerve activity (SSA) was recorded from the posterior cutaneous nerve of the forearm or radial nerve branches in 11 healthy volunteers. Skin electrical resistance and skin blood flow were recorded in the area innervated by the impaled nerve fascicle. Sudomotor nerve traffic and sweating was induced by whole body heating. Lower body negative pressure (LBNP) and tilting (3d? head up) was used for blood volume displacement from the chest to the lower body. Low levels of LBNP (5 and 10 mmHg) had no effect on blood pressure, heart rate or skin blood flow but induced a prompt inhibition of SSA and a reduced number of transient skin resistance changes (n= 9), both rapidly returning to control levels after cessation of LBNP. Quantitatively, the effect was similar at both levels of LBNP. Head up tilting also reduced SSA (n= 3, tilt manoeuvres). A capacity for mental stress-induced SSA increase remained during LBNP. Spontaneous flucturations in blood pressure did not affect SSA, arguing against arterial (high-pressure) baroreceptors modulating SSA. Consequently, the present results indicate that unloading of cardiopulmonary (low-pressure) volume receptors reduces sympathetic sudomotor nerve traffic and sweating in warm subjects. It is suggested that the reflex contributes to counteracting hypovolaemia.     

The articulo-cardiac sympathetic reflex in spinalized, anesthetized rats

Somatic afferent regulation of heart rate by noxious knee joint stimulation has been proven in anesthetized cats to be a reflex response whose reflex center is in the brain and whose efferent arc is a cardiac sympathetic nerve. In the present study we examined whether articular stimulation could influence heart rate by this efferent sympathetic pathway in spinalized rats. In central nervous system (CNS)-intact rats, noxious articular movement of either the knee or elbow joint resulted in an increase in cardiac sympathetic nerve activity and heart rate. However, although in acutely spinalized rats a noxious movement of the elbow joint resulted in a significant increase in cardiac sympathetic nerve activity and heart rate, a noxious movement of the knee joint had no such effect and resulted in only a marginal increase in heart rate. Because this marginal increase was abolished by adrenalectomy suggests that it was due to the release of adrenal catecholamines. In conclusion, the spinal cord appears to be capable of mediating, by way of cardiac sympathetic nerves, the propriospinally induced reflex increase in heart rate that follows noxious stimulation of the elbow joint, but not the knee joint.     

Modes of baroreceptor-sympathetic coordination

We tested the hypothesis that the cardiac-related rhythm in sympathetic nerve discharge (SND) results from the forcing of a central oscillator to the frequency of the heart beat by pulse-synchronous baroreceptor afferent nerve activity. For this purpose, time series analysis was used to examine the phase relations between the brachial arterial pulse (AP) and cardiac-related activity recorded from the postganglionic inferior cardiac sympathetic nerve (CN) in urethan-anesthetized cats. Specifically, we made cycle-by-cycle measurements of peak systolic blood pressure, heart period, CN burst amplitude, and the phase angle (and corresponding interval) between peak systole and the next peak of CN activity. As the steady-state level of systolic blood pressure was raised by increasing the rate of a constant intravenous infusion of phenylephrine, we observed transitions from no phase-locking of CN activity to the AP to either phase-locking of variable strength or phase walk through part of the cardiac-cycle on the time scale of respiration. Phase walk is defined as a progressive and systematic change in the phase lag of cardiac-related CN activity relative to peak systole. Raising blood pressure strengthened phase-locking and either increased or decreased the mean interval between peak systole and the next peak of CN activity even when the change in heart period was small. CN burst amplitude and the interval between peak systole and the next peak of CN activity were inversely related, but the strength of the relationship varied considerably with experimental conditions. The relationship was strongest during phase walk. Step-wise increases in blood pressure induced by abdominal aortic obstruction led to an abrupt increase in the phase lag of CN activity relative to peak systole even when heart rate was not changed. We refer to such changes as sharp phase transitions that are a general property of dynamical nonlinear systems. The results support the view that the cardiac-related rhythm in SND is a forced nonlinear oscillation rather than the consequence of periodic inhibition of randomly generated activity.     

Autonomic responses to lateralized cold pressor and facial cooling tasks

Asymmetry in central nervous system (CNS) control of autonomic nervous system (ANS) activity, a widely debated topic, was investigated via lateralized presentation of two ANS challenges: cold pressor, which elicits primarily sympathetic activation, and facial cooling, a predominantly vagal task. Seventy‐three university students (37 female) engaged in these tasks while cardiovascular and electrodermal measures were acquired. Compared to right‐side cold pressor, left cold pressor elicited generally larger cardiac, blood pressure, and skin conductance responses, but did not evoke asymmetric changes in heart rate variability. Facial cooling elicited significant increases in vagally mediated heart rate variability, but they were also not lateralized. These findings are consistent with reports of right hemisphere dominance in sympathetic regulation, but indicate that CNS vagal control is relatively symmetric. These results are framed in terms of polyvagal theory and neurovisceral integration two influential models of CNS‐ANS integration in the service of adaptive environmental engagement.     

Cardiac sympathetic adrenergic pathways in which synaptic transmission is blocked by atropine sulphate

1. Stimulation of the thoracic sympathetic nerve trunk caused a rise in arterial blood pressure and heart rate which was reduced but not abolished during the infusion of hexamethonium chloride, pentolinium tartrate, mecamylamine or tetraethylammonium chloride.

2. Preganglionic stimulation no longer elicited a synchronous sC elevation in the post-ganglionic nerves. The persistent blood pressure and heart rate response was associated with an asynchronous discharge in these nerves.

3. Both the persistent response and the asynchronous discharge were abolished by the intravenous injection of atropine sulphate in doses of 30 μg/kg.

4. Atropine had no effect on spike amplitude or shape, conduction velocity or frequency response in either the pre- or post-ganglionic nerve trunks. Nor did it affect the rise in blood pressure and heart rate evoked by stimulation of the post-ganglionic cardiac sympathetic nerves.

5. It is concluded that atropine partially blocked synaptic transmission in cardiac sympathetic adrenergic pathways.

     

Reflex changes in sympathetic nerve activity during mechanical ventilation with PEEP in sino-aortic denervated rats

The aim of this study was to evaluate the role of cardiopulmonary receptors with vagal afferents in the reflex control of sympathetic nerve activity during mechanical ventilation with positive end-expiratory pressure (PEEP). Experiments were performed on 17 chloralose-anaesthetized rats. Changes in renal sympathetic nerve activity (RSNA), heart rate and mean arterial pressure were studied at zero end-expiratory pressure (ZEEP) and at 5 and 10 cm H2O PEEP in intact animals (n = 8), after sino-aortic denervation (n = 17) and after sino-aortic denervation plus vagotomy (n = 10). In the intact animals, 10 cm H2O PEEP induced a significant increase in RSNA (+66%) and heart rate (+10%) while the mean arterial pressure did not change significantly. Sino-aortic denervation increased baseline levels of RSNA, heart rate and mean arterial pressure. After sino-aortic denervation, 10 cm H2O PEEP still induced a significant increase in RSNA (+22%) and heart rate in 13 animals. In four animals, 10 cm H2O PEEP elicited a depressor reflex with a significant decrease in both RSNA (-32%) and heart rate. Bilateral vagotomy after sino-aortic denervation at ZEEP significantly increased RNSA (+15%) and heart rate, indicating an ongoing tonic inhibitory influence on RSNA from vagal afferents in sino-aortic denervated rats. The PEEP did not induce any significant change in RSNA or heart rate after sino-aortic denervation plus vagotomy. The results indicate that cardiopulmonary receptors with vagal afferents contribute to the reflex excitation of the sympathetic nervous system during mechanical ventilation with PEEP. Under certain circumstances, PEEP may also trigger powerful depressor reflexes, mediated by vagal afferents.     

Sympathetic transients caused by abrupt alterations of carotid baroreceptor activity in humans

We examined the role of carotid baroreceptors in the short-term modulation of sympathetic outflow to the muscle vascular bed and parasympathetic outflow to the heart in 10 healthy adults. Afferent carotid baroreceptor activity was modified with 30-mmHg neck suction or pressure applied during held expiration, and efferent sympathetic activity was measured with microelectrodes inserted percutaneously into peroneal nerve muscle fascicles. Sympathetic responses were conditioned importantly by directional changes of carotid transmural pressure: increased pressure (onset of neck suction or offset of neck pressure) inhibited (totally) sympathetic activity, and reduced pressure (offset of neck suction or onset of neck pressure) augmented sympathetic activity. Responses occurred after a latency of about 2 s and did not persist as long as changes of neck-chamber pressure. Cardiac intervals were prolonged by increased carotid transmural pressures and shortened by decreased carotid transmural pressures, but, in contrast to sympathetic responses, cardiac responses adapted only slightly during neck-chamber pressure changes. Our results suggest that in the human a common baroreceptor input is processed differently in central vagal and sympathetic networks. Muscle sympathetic responses to changing levels of afferent baroreceptor traffic are profound but transitory. They appear to be conditioned more by changes of arterial pressure than by its absolute levels.     

Renal nerve activity and exaggerated natriuresis in conscious spontaneously hypertensive rats

Exaggerated natriuresis upon volume loading occurs in both human and animal hypertension and is mainly due to suppressed tubular reabsorption. To explore whether altered renal sympathetic activity contributes to this response, conscious male spontaneously hypertensive rats (SHR) were exposed to isotonic saline loading in comparison with normotensive male Wistar Kyoto rats (WKR). After a 60 min control hydropenic period, during which mean arterial pressure, heart rate, renal sympathetic nerve activity and urinary sodium excretion were followed, a 60 min period of intravenous volume expansion with isotonic saline (0.2 ml/minx 100 g b. w.) was started followed by a 60 min hydropenic recovery period. Already during the control period sodium excretion was significantly higher in SHR. During the volume load and subsequent recovery period a clearly exaggerated natriuresis occurred in SHR compared with WKR. Further, volume loading reduced renal sympathetic nerve activity in all animals, but significantly more in SHR. Moreover, volume loading reduced mean arterial pressure and heart rate in both groups. It is suggested that the accentuated reflex inhibition of renal sympathetic activity in SHR upon volume loading emanates from cardiac mechanoreceptors and partly explains the exaggerated natriuresis in SHR. This augmented ‘volume’ reflex response is probably due to reduced systemic venous compliance in SHR with a consequently increased central filling and cardiac receptor activation.     

Reflex Inhibition of Sympathetic Nerve Activity by Phenoxybenzamine

The effects on baroreceptor and sympathetic nerve activity of the a-adrenergic blocking agent phenoxybemamirie have been investigated in 13 anesthetized rabbits. Nerve activities were recorded at various blood pressure levels, obtained by stepwise changes of blood volume. With phenoxybenzamine, aortic nerve activity at 80 and 90 mm Hg exceeded control values by 66 and 62 %. At the same pressures, renal nerve activity was reduced by 30 and 55 %. Although blood pressure started to fall shortly after injecting the drug, about 20 min elapsed before development of maximum effects on the nerves. When studied during stepwise changes of blood pressure after a similar period of hypotension—but without the drug-sympathetic nerve activity had increased. Phenoxybenzamine had accordingly effected a suppression of sympathetic activity, suggesting that the hypotensive response to phenoxybenzamine is aided by increased reflex inhibition of sympathetic nerve activity.     

Effect of diazepam on endocrine and cardiovascular responses to head-up tilt in humans

Effects of the GABAergic drug diazepam (0.15 mg kg^-1, i.v.) on cardiovascular and endocrine responses to 50± head-up tilt were evaluated in seven men. During the initial phase of tilt (normotensive phase), increases in heart rate (HR) and total peripheral resistance (TPR) and decreases in cardiac output were unaffected by diazepam. Also the associated increase in plasma noradrenaline did not change, while response in plasma ACTH was diminished and in plasma cortisol abolished by diazepam (F(1, 10) = 6.45; P < 0.03). After 42 ± 4 min of sustained tilt with saline (control) and 47 ± 6 min (n.s.) after diazepam, presyncopal symptoms appeared (hypotensive phase) associated with decreases in HR, MAP, and TPR (P < 0.01). This episode induced a 2–3-fold increase in plasma ACTH, β-endorphin, prolactin, cortisol (< 0.01), and a moderate increase in plasma adrenaline (P < 0.05). Diazepam did not significantly change cardiovascular and endocrine responses to the hypotensive phase of tilt. Results indicate that diazepam attenuates the cortisol part of pituitary-adrenal responses to moderate, but not to severe, central hypovolaemia in humans with no effect on cardiovascular tolerance.     

下丘脑室旁核小电导钙激活钾通道过表达降低慢性心衰大鼠肾交感神经兴奋性

 目的：研究下丘脑室旁核小电导钙激活钾通道亚型2（SK2）过表达对慢性心衰大鼠心率、血压和肾交感神经活性的影响,揭示心衰大鼠下丘脑室旁核对交感系统的调节机制。方法：构建SK2重组腺病毒穿梭载体pDC316-mCMV-EGFP-rKCNN2。采用SD大鼠,手术组用左冠状动脉前降支结扎术制作慢性心衰模型,假手术组大鼠左冠状动脉前降支下穿线但不结扎,术后6周用超声心动图测定心功能。心衰组和假手术组分别在室旁核微量注射 SK2 腺病毒pDC316-mCMV-EGFP-rKCNN2和对照腺病毒pDC316-mCMV-EGFP,7 d后通过超声心动图检测心功能的改变;运用免疫组织化学、RT-PCR和Western blotting方法检测SK2重组腺病毒转染情况及表达。室旁核微量注射SK通道阻滞剂apamin,通过PowerLab 8/30系统采集信号记录心率、血压和肾交感神经活性的变化。结果: 心衰大鼠SK2表达较假手术组减少,下丘脑室旁核微量注射SK2腺病毒导致心衰大鼠肾交感神经兴奋性明显降低,下丘脑室旁核微量注射对照腺病毒对假手术大鼠交感神经兴奋性的改变不明显。结论：SK通道蛋白在心衰状态下表达降低并可能导致其功能减弱,进而促成由SK2通道介导的中枢负性交感调节通路的降低,增加了交感神经兴奋性,从而加重心衰的发展。SK2过表达减弱了心衰大鼠的肾交感神经活性,为治疗心衰提供了新的方向。     

Influence of intravenous infusion on heart rate, sympathetic and vagal efferentation and left atrial and aortic baroreceptor activity in dogs

The influence of 42 i.v. infusions of saline on heart rate, sympathetic and vagal cardiac efferent activity and on the aortic baroreceptor and left atrial B-type nerve impulse activity was studied in 32 morphine-chloralose anesthetized dogs. The responses in heart rate were tachycardic in 31 infusions and bradycardic in 11 infusions. In tachycardia, sympathetic activity increased in a majority of the cases but also decreases and nonsignificant changes were observed. Vagal efferentation decreased in most of the cases but also nonsignificant changes or increases in activity occurred. Sympathetic efferentation mainly decreased in bradycardic responses while vagal efferentation diverged in different directions in its nerve activity rate. The ratio of sympathetic to vagal impulses significantly correlated to the heart rate in most of the cases in tachycardia but not in bradycardia. It is concluded that sympathetic and vagal cardiac efferentation plays a significant role in heart rate regulation in volume load-induced tachycardia but in bradycardia only the changes in sympathetic cardiac efferentation are important in respect to heart rate changes. The aortic baroreceptor and left atrial B-type receptor activity rate increased both in tachycardia and bradycardia. Changes in the activities of these receptors do not explain the different heart rate responses. It is supposed that bradycardic responses result from changes in cardiac contraction associated with some reflex mechanism suppressing the excitatory influence of the activity of atrial receptors on sympathetic cardiac efferentation.     

Autonomic cardiovascular control during submergence and emergence in bullfrogs.

Unanesthetized bullfrogs were involuntarily submerged for 25 min in air-saturated water at 21 degrees C. Significant bradycardia was observed while systemic blood pressure was maintained or slightly elevated. Upon emergence, heart rates immediately returned to presubmergence levels or higher. Similar responses were observed in frogs allowed to make voluntary dives in an experimental tank. Heart rates of vagal-blocked (atropine) frogs did not change during submergence or emergence. beta-Adrenergic blockade (propranolol) had little effect on the magnitude of heart rate decrease during submergence or its increase upon emergence. After alpha-adrenergic blockade (phentolamine), frogs developed diving bradycardia while undergoing a fall in systemic blood pressure. It is concluded that, in bullfrogs, 1) bradycardia during submergence is entirely due to increased vagal activity, 2) the immediate cardiac rate increase upon emergence apparently results from a decrease in vagal tone; and 3) there appears to be no substantial reciprocal sympathetic influence on heart rate during alterations in vagal tone.