The yin and yang of cardiac autonomic control: Vago-sympathetic interactions revisited

We review the pattern of activity in the parasympathetic and sympathetic nerves innervating the heart. Unlike the conventional textbook picture of reciprocal control of cardiac vagal and sympathetic nervous activity, as seen during a baroreceptor reflex, many other reflexes involve simultaneous co-activation of both autonomic limbs. Indeed, even at ‘rest’, the heart receives tonic drives from both sympathetic and parasympathetic cardiac nerves. Autonomic co-activation occurs during peripheral chemoreceptor, diving, oculocardiac, somatic nociceptor reflex responses as well as being evoked from structures within the brain. It is suggested that simultaneous co-activation may lead to a more efficient cardiac function giving greater cardiac output than activation of the sympathetic limb alone; this permits both a longer time for ventricular filling and a stronger contraction of the myocardium. This may be important when pumping blood into a constricted vascular tree such as is the case during the diving response. We discuss that in some instances, high drive to the heart from both autonomic limbs may also be arrhythmogenic.     

Autonomic nerve and cardiovascular responses to changing blood oxygen and carbon dioxide levels in the rat

Contribution of autonomic nervous system activity to the heart rate and blood pressure responses during chemoreceptor excitations by systemic hypoxia and hypercapnia and to hyperoxia and hypocapnia was analyzed in the urethane-anesthetized, artificially ventilated rats. Systemic hypoxia induced a co-activation of two antagonistic nerves: an increase in cardiac sympathetic and in cardiac vagal efferent nerve discharges. Increased heart rate was due to predominance of the cardiac sympathetic over the cardiac vagal activation. In spite of a marked reflex increase in the renal and cardiac sympathetic nerve activities, the local vasodilator effect of hypoxia prevented consistent changes in arterial blood pressure. Bilateral section of the carotid sinus nerves (CSN) mostly abolished autonomic nerve responses and produced a profound decreases in the blood pressure during hypoxia. Hyperoxia elicited a pressor response due to peripheral vasoconstriction with no significant change in the autonomic nerve activities except for a decrease in the cardiac sympathetic nerve discharges. Hypercapnia significantly increased blood pressure and renal nerve sympathetic activity. In contrast to hypoxia, hypercapnia excited cardiac sympathetic and inhibited cardiac vagal activity. This reciprocal effect did not elicit neurogenic cardioacceleration, because it was masked by the local inhibitory action of CO2 on the heart rate. The increase in sympathetic activities and in blood pressure during hypercapnia persisted after bilateral CSN section indicating that the responses were mediated by central rather than by peripheral chemoreceptors. Hypocapnia produced a significant increase in cardiac vagal discharges yet a cardioacceleratory response occurred due to the local effect upon heart rate. The present results indicate that in the rat, autonomic nervous responses differ depending on the type, i.e. hypoxic or hypercapnic, chemoreceptor stimuli. Reflex heart rate and blood pressure responses do not follow the autonomic nerve activities exactly. Circulatory responses are greatly modified by local peripheral effects of hypoxic, hyperoxic, hypocapnic or CO2 stimuli on the cardiovascular system. Species differences characterizing the autonomic nerve responsiveness to chemical stimuli in the rat are described.     

Efferent discharges of sympathetic and parasympathetic nerve fibers during increased intracranial pressure in anesthetized cats in the absence and presence of pressor response

Efferent discharges of the cervical sympathetic cardiovascular and vagal type 1 fibers in response to increased intracranial pressure (ICP) were simultaneously recorded in cats anesthetized with pentobarbitone and ventilated artificially. Sympathetic outflow of renal nerve fibers was also recorded in some animals. The type 1 fibers were assumed to be cardiac vagal fibers, from the response behavior such a pulse-synchronicity to respiratory and heart rhythm, reflex activation from arterial baroreceptors and reciprocal relationship of the activity to sympathetic ones during slower fluctuations of hemodynamic changes, and which occur spontaneously during Mayer waves. The vagal type 1 discharges increased to various amplitudes with increase in ICP and in the absence and the presence of pressor response. Efferent outflow of the renal and cervical sympathetic fibers frequently decreased with a moderate increase in ICP. There was a slight decrease or no apparent change in the blood pressure, and a higher elevation of ICP ensued. Heart rates decreased with increase in ICP, while the rate frequently increased with levels of ICP over about 120 mm Hg. Changes in the vagal and sympathetic discharges always began at a time before the initiation of cardiovascular response to the elevated ICP. However, when ICP was repeatedly increased, the increase in vagal discharges progressively decayed and was accompanied by vigorous sympathetic firings and a marked pressor response. The sympathetic outflow also decayed following the decrease in vagal activities. The present findings of changes in the vagal type 1 discharges demonstrate clear participation of parasympathetic as well as sympathetic nerve activity in the occurrence of cardiovascular responses to increased ICP. Changes in both these autonomic nerve responses may explain the initial fall in arterial blood pressure and pressor responses associated with bradycardia or tachycardia, at different levels of elevated ICP.     

Split medulla preparation in the cat: arterial chemoreceptor reflex and respiratory modulation of the renal sympathetic nerve activity

The study was undertaken in order to assess the changes in sympathetic output in a split medulla preparation of the cat which, as shown earlier, has impaired respiratory rhythm generation. The effects of medullary midsagittal sections on renal sympathetic nerve firing were investigated in chloralose anesthetized, paralyzed and artificially ventilated cats. Recordings of phrenic and recurrent laryngeal nerve activity served as indices of central respiratory rhythm generation. Sections, 5 mm deep from the dorsal medullary surface and extending 6 mm rostrally and 3 mm caudally to the obex, did not produce any significant changes in heart rate, blood pressure or tonic renal sympathetic nerve firing levels. They decreased or abolished, however, the respiratory rhythmicity in renal sympathetic nerve which paralleled the reduction of inspiratory discharges in phrenic and recurrent laryngeal nerves, and abolished the carotid body chemoreceptor-sympathetic reflex. The inspiratory activity remaining after the sections could still be enhanced by chemoreceptor stimulation. The inhibitory baroreceptor and pulmonary stretch receptor sympathetic reflexes, and the central excitatory effect of CO2 on renal sympathetic nerve firing were not altered. The effects of electrical stimulation within the midsagittal plane of the medulla have shown that descending pathways from the medullary inspiratory neurons (or their medullary collaterals) do not participate in the facilitation of spinal preganglionic neurons during inspiration and in relaying the pulmonary stretch receptor inhibitory sympathetic reflex. A region located close to the obex was identified from which excitatory responses in renal sympathetic nerves, compatible with the response obtained by carotid sinus nerve stimulation, could be evoked. It is concluded that a lesion in the midline of the lower medulla at the level of the obex selectively destroys cells or pathways which relay the carotid body chemoreceptor-sympathetic reflex.     

Dynamic changes in baroreceptor-sympathetic coupling during the respiratory cycle

In urethane-anesthetized, paralyzed, and artificially ventilated cats, we observed an unusual form of "phase walk" of the cardiac-related burst of inferior cardiac postganglionic sympathetic nerve discharge (SND) relative to the systolic phase of the arterial pulse (AP) and thus pulse-synchronous baroreceptor nerve activity. Unlike classic phase walk ascribable to weakened coupling (desynchronization) of two oscillators, AP-SND phase walk was characterized by epochs of progressive, bidirectional changes in the angle of strong coupling (AP-SND coherence values, >0.9) of these signals that recurred on the time scale of the respiratory cycle and whose range was approximately one third of the period of the heart beat. AP-SND phase walk was linked to two respiratory variables (central respiratory drive and vagal lung inflation afferent activity) as demonstrated by the following observations. First, in five normocapnic cats (end-tidal CO(2), 4.3 +/- 0.2%) with intact vagus nerves and three vagotomized cats, AP-SND phase walk was characterized by a progressive heart-beat-to-heart-beat decrease in the lag of SND relative to the AP during the inspiratory phase of phrenic nerve activity and an increase in the lag during the expiratory phase. Second, in three cats with intact vagus nerves that were hyperventilated (end tidal CO(2), 1.6 +/- 0.4%) to phrenic nerve quiescence, the lag of the cardiac-related burst of SND relative to the AP increased during lung inflation and decreased during lung deflation. Additional experimentation revealed that AP-SND phase walk is attributable to respiratory-induced changes in the frequency of the centrally generated sympathetic nerve rhythm rather than heart rate. Moreover, the data demonstrate that the frequency and amplitude of the sympathetic oscillation are independently controlled by the above mentioned respiratory parameters.     

Effects of taste stimulation on the efferent activity of the autonomic nerves in the rat

Effects of taste stimulation on the efferent discharges in the pancreatic and hepatic branch of the vagus nerve, and those in the adrenal, pancreatic and hepatic branch of the splanchnic nerve, and the sympathetic nerve innervating interscapular brown adipose tissue, were observed in the anesthetized rat. Sweet taste stimulation with 5% glucose or 10% sucrose caused an increase in activity of pancreatic and hepatic branch of the vagus nerve and brown adipose tissue nerve, and a decrease in discharge rate of the adrenal, pancreatic and hepatic branch of the splanchnic nerve. Salty taste stimulation with 5% NaCl resulted in opposite effects in these nerves. Results suggest preabsorptive reflex control of visceral functions due to taste stimulation.     

Central action of alpha-adrenoceptor agents on the baroreceptor reflex.

In chloralose-anaesthetized cats the effects of intravenous application of the alpha 1- and alpha 2-adrenoceptor agonistic and antagonistic agents methoxamine, prazosin, B-HT 933 and rauwolscine were tested on baroreceptor reflex, sympathetic background activity and blood pressure. Sympathetic activity was recorded from the renal nerve and the efficacy of the central transmission of the baroreceptor reflex was measured by the duration of the complete inhibition of renal nerve activity during electrical stimulation of the left carotid sinus nerve. All baroreceptors were denervated by sectioning both carotid sinus and vagal nerves. The alpha 1-agonist methoxamine increased baroreceptor-induced sympatho-inhibition, sympathetic background activity and blood pressure. The alpha 1-antagonist prazosin had the opposite effects. The alpha 2-agonist B-HT 933 was most effective in augmenting the inhibitory response in sympathetic activity to baroreceptor stimulation; sympathetic background activity and blood pressure were also decreased. At low doses (50 micrograms/kg) the alpha 2-antagonist rauwolscine reduced the baroreceptor sympathetic reflex inhibition and increased sympathetic activity and blood pressure. The effect of B-HT 933 upon the baroreceptor reflex could be completely antagonized by rauwolscine. These findings demonstrate a very effective facilitation of the baroreceptor reflex transmission by stimulation of central alpha 2-adrenoceptors. Through such humoral-neuronal interaction circulating catecholamines are likely to modulate cardiovascular control.     

Effects of middle cerebral artery occlusion on baroreceptor reflex control of heart rate in the rat

Neurons in the insular cortex have recently been shown to innervate medullary autonomic nuclei such as the nucleus tractus solitarii (NTS). The present study examines the effect of lesioning the insular cortex on baroreceptor-heart rate reflex in conscious rats. We did this by occluding the stem of the left proximal middle cerebral artery which causes a lesion of the insular and adjacent lateral frontoparietal cortices. Nine and 10 days after lesioning or sham operation, reflex heart rate responses were recorded following i.v. doses of the pressor agent phenylephrine and the depressor agent sodium nitroprusside. Baroreceptor reflex parameters were determined by computerized sigmoidal curve-fitting. The overall contribution of the sympathetic and the cardiac vagus were assessed by using peripherally acting muscarinic and beta-adrenoceptor antagonists, respectively. Lesioned rats were compared to sham-operated rats. Lesioning the insular cortex did not affect mean blood pressure and heart rate. However, the lesion selectively enhanced reflex vagal bradycardia that occurred when mean blood pressure was artificially elevated. A greater vagal bradycardia with no change in the upper plateau indicated that ischemia was acting entirely on the baroreflex-dependent vagal cardiac motoneurons. There was no effect on the sympathetic heart rate range but the normalized gain of the sympathetic component was increased in those lesioned rats. These observations suggest that the unilateral cortical lesion chronically affected the baroreceptor control of heart rate through mechanisms differentially affecting the vagus and the cardiac sympathetic nerves.     

An anomalous vagorenal reflex pathway in the cat

Although physiological investigations support the view that the innervation to the kidney is primarily sympathetic in origin, there is anatomic evidence suggesting direct vagal projections to the kidney. We examined electrophysiologically the possibility that neural connections exist between the cervical vagus and renal nerves. Electrical stimulation of the peripheral segment of the cut cervical vagus evoked electrical activity in the central segment of cut renal nerve of chloralose-anesthetized, paralyzed cats. The evoked potentials (vagorenal responses) displayed components with peak latencies of about 50, 120, and 500 ms. Another peak at about 175 ms was also seen in some cases. In addition, a period of postexcitatory depression occurred between approximately 180 and 400 ms after delivery of the stimulus. Evoked responses were recorded in the contralateral as well as the ipsilateral renal nerves. In contrast, stimulation of the central cut end of renal nerves did not elicit responses in the cervical vagus. Vagorenal responses were not altered by cutting the subdiaphragmatic vagus indicating that the abdominal vagus was not involved in this response. Electrical activity in renal nerves elicited by vagal stimulation could be eliminated by either ganglionic blockade or by cutting or cooling the splanchnic nerves. Finally, supraspinal ischemia abolished the vagorenal response. These data suggest that a vagorenal reflex pathway exists and that the potentials recorded in renal nerves are due to activation of aberrant sensory fibers traveling from the peripheral segment of the cut cervical vagus to the central nervous system, where they excite a sympathetic efferent pathway to the kidney.     

Anatomical feasibility of vagus nerve esophageal branch transfer to the phrenic nerve

This study measured the vagus and phrenic nerves from 12 adult cadavers. We found that the width and thickness of the vagus and phrenic nerves were different in the chest. The distance from the point of the vagus nerve and phrenic nerve on the plane of the inferior border of portal pulmonary arteries (T point) was approximately 7 cm to the diaphragm and was approximately 10 cm to the clavicle level. The number of motor fibers in the vagus nerves was 1 716 ± 362, and the number of nerve fibers was 4 473 ± 653. The number of motor fibers in the phrenic nerves ranged from 3 078 ± 684 to 4 794 ± 638, and the number of nerve fibers ranged from 3 437 ± 642 to 5 071 ± 723. No significant difference was found in the total number of nerve fibers. The results suggest that width, thickness, and total number of nerve fibers are similar between the vagus and phrenic nerves, but the number of motor fibers is different between them.     

Effect of cardiac vagal and sympathetic nerve activity on heart rate in rhythmic fluctuations

Beat-to-beat changes observed in cardiac vagal and sympathetic nerve activity and their effects on cardiac cycle length were studied during slow wave blood pressure and heart rate fluctuations (third order rhythm) and during respiratory sinus arrhythmia. Recordings were made from both nerves simultaneously in chloralose anesthetized and artificially ventilated dogs. During slow wave fluctuations in heart rate, a linear relationship was found to exist between the number of spikes per pulse interval recorded from vagal and sympathetic nerves and the length of pulse intervals. During respiratory sinus arrhythmia the time course of rhythmic changes in nerve activity and in cardiac cycle length was analyzed. Comparison of time courses indicated that vagal discharges affected the timing of not the following beat, but the one after; while the sympathetic effect was further delayed, affecting the third beat after the discharge. Baroreceptor stimulation, which resulted in lengthening the cardiac cycle, shifted this relationship by one cycle, i.e. vagal discharges affecting the occurrence of the following beat, while sympathetic discharges affecting the beat after. These results provide evidence for the conclusion that in dogs both vagal and sympathetic nerve activity contribute to the control of cardiac cycle length, however, with different time relations and effectiveness.     

Reflex effects on renal nerve activity and renal vascular tone during occlusion of superior mesenteric artery in anesthetized dogs

This study was designed to evaluate the contribution of the systemic baroreceptor reflex on renal nerve activity (RNA) and renal vascular resistance (RVR) during occlusion of the superior mesenteric artery (SMAO) in anesthetized dogs. Animals were divided into two groups; RVR evaluated group and RNA measured group. For evaluation of changes in RVR, the left kidney was perfused at a constant flow with heparinized blood by using a pulsatile roller pump. Renal perfusion pressure, arterial blood pressure and heart rate were measured simultaneously. During SMAO, MAP and RVR increased significantly in animals with intact systemic baroreceptors. After combined denervation of the carotid sinus and vagal nerves, a significant enhancement of this RVR response during SMAO occurred and the level of changes in RVR were significantly greater than those in animals with an intact neuraxis. In the RNA measured group, renal sympathetic nerve activity, arterial blood pressure and heart rate were measured simultaneously before and during SMAO. During SMAO, MAP and RNA increased significantly in animals with intact systemic baroreceptors. These MAP and RNA responses to SMAO were significantly enhanced in animals with combined denervation of the carotid sinus and vagal nerves. These results indicate that SMAO evokes an increase in arterial blood pressure, renal sympathetic nerve activity and renal vascular resistance. The reflex increase in renal nerve activity and renal vascular tone during SMAO is modified and minimized by an activation of systemic baroreceptors.     

Gustatory-salivary reflex: neural activity of sympathetic and parasympathetic fibers innervating the submandibular gland of the hamster

Electrophysiological experiments were performed to clarify the neural control mechanisms subserving gustatory-salivary reflex in anesthetized and decerebrate hamsters. Efferent neural activities of postganglionic sympathetic and preganglionic parasympathetic fibers, innervating the submandibular gland, were recorded when taste stimuli were infused into the oral cavity. Neural activities of primary gustatory afferents were also recorded from the chorda tympani (innervating the anterior part of the tongue) and the glossopharyngeal nerve (innervating the posterior part of the tongue). The parasympathetic fibers showed a low rate of spontaneous discharges (about 0.3 Hz), and responded tonically in an excitatory manner to taste stimulation. The magnitude of parasympathetic activity was highly correlated with the magnitude of gustatory afferent responses of the chorda tympani rather than that of the glossopharyngeal nerve. On the other hand, the sympathetic fibers showed irregular burst discharges (1.5 burst/s), and the rate of burst discharges was increased in response to high concentrations of HCl (0.03 M) or NaCl (1 M) solutions. Deafferentation experiments suggest that the parasympathetic activity is mainly influenced by gustatory information via the chorda tympani, while the sympathetic activity can be evoked by both the chorda tympani and glossopharyngeal nerve.     

An analysis of reflex changes in excitability of phrenic,laryngeal, and intercostal motoneurons

An investigation was carried out in anesthetized cats to ascertain whether self-excitation of phrenic motoneurons is a specific or generalized reflex mechanism for motoneurons allied to respiration. Whereas stimulation of only caudal intercostal nerves evoked discharge of phrenic motoneurons (intercostal-to-phrenic reflex), stimulation of all intercostal nerves elicited discharges in the recurrent laryngeal nerve (intercostal-to-recurrent laryngeal reflex). Weak superior laryngeal nerve stimulation provoked short-latency discharges in the recurrent laryngeal nerve but inhibited on-going inspiratory activity in phrenic and external intercostal motoneurons. In the presence of self-excitation of phrenic motoneurons (phrenophrenic system), there was concomitant excitation of laryngeal motoneurons. In contrast, when self-excitation of laryngeal motoneurons occurred (laryngolaryngeal system) there was concomitant inhibition of inspiratory activity (phrenic and external intercostal motoneurons). Paired shocks delivered to superior laryngeal and intercostal nerves while recording from phrenic, recurrent laryngeal, and intercostal nerves failed to reveal convergent interaction. It is concluded that self-excitation is a generalized reflex mechanism for certain motoneurons allied to respiration.     

Antidromic activation of vagal and sympathetic afferents does not produce intestinal contractions in dogs.

The question has been asked whether vagal and sympathetic afferents activated antidromically play a role as motor nerves on the in vivo small intestine in dogs anesthetized with urethane. The vagus nerve of one side was cut above the nodose ganglion and the efferent fibers allowed to degenerate. Peripheral stimulation (5-50 Hz, 0.5-3 ms, 5-25 V) of an intact cervical vagus, being able to excite both efferent and afferent fibers, caused large contractions in the jejunum and stomach, whereas stimulation of the contralateral cut cervical vagus could not produce any response in the jejunum but small contractions in the stomach. Peripheral stimulation of the cut cervical vagus did not produce bradycardia and hypotension. Single- and multi-unit discharges to distension of the jejunal segments could be recorded from the peripheral cut end of the cut cervical vagus. Immunohistochemically, there were many substance P-containing cells in both nodose ganglia. Antidromic stimulation of the dorsal roots (T7-T10) did not induce any response in the jejunum but contractions in the stomach. The results may confirm that vagal and sympathetic afferents have no antidromic motor function at least in the in vivo canine small intestine.     

Control of the heart rate by sympathetic nerves in cats

Pre- and postganglionic sympathetic nerves were electrically stimulated and heart rate was recorded in chloralose-anaesthetised cats. The vagal nerves and white rami were cut on both sides. Electrical stimulation was performed with a 15- or 30-s train of 0.2-ms pulses at a frequency of 30 Hz. The control heart rate was 150 beats/min. Heart rate was increased when the T3 white ramus on the left (52 beats/min above control) and T3, T4 white rami on the right side (100 beats/min above control) were stimulated electrically. The magnitude of the heart rate increase declined when the neighbouring thoracic white rami were stimulated. The increase of the heart rate was caused by group B preganglionic fibres. Electrical stimulation of the sympathetic fibres in the right vagus nerve and the right inferior cardiac nerve increased the heart rate by 92 beats/min and by 67 beats/min above the control level respectively. Electrical stimulation of the left inferior cardiac nerve, the left middle cardiac nerve and the sympathetic fibres in the left vagus nerve resulted in an increase of the heart rate of 43 beats/min, 30 beats/min and 49 beats/min from the control level respectively. This indicates that a majority of the preganglionic cardiac sympathetic fibres, whose activity influences the heart rate, originate from the T3 and T4 segments of the spinal cord. The majority of the postganglionic cardiac sympathetic fibres which affect the heart rate are located in the vagal nerves.     

Obstructive sleep apnoea and the autonomic nervous system

Understanding of the pathophysiology of obstructive sleep apnoea, a common yet relatively newly recognized condition, has advanced rapidly in recent years. This condition produces major acute haemodynamic changes and causal relationships with hypertension and cardiovascular morbidity have been proposed. The role that the autonomic nervous system plays in mediating these cardiovascular changes has been the focus of intensive research activity and the development of few techniques in physiological monitoring, such as spectral analysis of heart rate variability, Finapres blood pressure monitoring, measurement of muscle sympathetic nerve activity, radionuclide tests and animal models of obstructive sleep apnoea have substantially increased the knowledge base. The acute haemodynamic changes are associated with high levels of sympathetic discharge and with fluctuating parasympathetic activity. There are also chronic changes in baroreceptor and chemoreceptor reflexes associated with an increase in baseline daytime sympathetic activity and abnormal vagal reflex responses to voluntary respiratory manoeuvres. These acute autonomic changes appear to be provoked by a combination of stimuli triggered by hypoxaemia, upper airway responses, ventilatory changes and arousal. The mechanisms of the chronic autonomic changes are less clear; it is likely that recurrent hypoxaemia is important, but the roles of recurrent ventilatory stress and arousal are not clear. Normalizing respiration with CPAP therapy prevents the acute cardiovascular changes and reduces the acute sympathetic over-activity, and in compliant patients, restores abnormal vagal responses to normal and reduces excess chronic sympathetic activity. Whether or not this produces a reduction in long-term cardiovascular morbidity is not established.     

Reflex control of the gastric motility by the vagus and splanchnic nerves in the guinea pig in vivo

Gastric responses to electrical stimulation of the vagus and splanchnic nerves and to esophageal distension were observed in studies of the reflex control of the gastric motility in anesthetized guinea pigs in vivo. The gastric motility was inhibited by both vago-vagal and splanchno-vagal reflexes through the activation of non-adrenergic inhibitory nerve fibers and by splanchno-splanchnic reflex through the inactivation of the intramural cholinergic excitatory neurons. Distension of the lower esophagus caused a relaxation of the stomach which was mediated by an intrinsic reflex via intramural non-adrenergic inhibitory neurons. Furthermore, stimulation of the splanchnic nerve innervating the stomach seems to activate adrenergic inhibitory, cholinergic excitatory and probably some non-adrenergic inhibitory fibers.     

Reflex control of sympathetic outflow and depressed baroreflex sensitivity following myocardial infarction

Reflex control of heart rate is frequently impaired following myocardial infarction. This is referred to as depressed baroreflex sensitivity. The aim of these experiments was to assess the function of other autonomic reflexes in dogs with depressed baroreflex sensitivity. Comparisons were made to dogs in whom baroreflex sensitivity was preserved or unchanged after myocardial infarction. Under chloralose-barbiturate anesthesia, reflex control of sympathetic outflow by the sinoaortic baroreceptors was determined by measurement of changes in systolic arterial pressure and efferent renal sympathetic nerve activity during infusion of phenylephrine. Following sinoaortic denervation, reflex control of sympathetic outflow by cardiac receptors with vagal afferent fibers was determined by measurement of changes in pulmonary capillary wedge pressure and renal nerve activity during blood volume expansion. Reflex decreases in renal nerve activity in response to increases in arterial pressure were similar in the two groups of dogs. In contrast, elevation of pulmonary capillary wedge pressure elicited significantly greater reflex decreases in renal nerve activity in dogs with depressed baroreflex sensitivity following myocardial infarction compared to dogs with preserved baroreflex sensitivity. Hemodynamic parameters and infarct sizes were similar in each group. In conclusion, activation of cardiac receptors with vagal afferent fibers elicited greater reflex inhibition of sympathetic outflow in dogs with depressed baroreflex sensitivity following myocardial infarction. These data suggest that these receptors are "sensitized". These results provide additional support for the hypothesis that depressed reflex control of heart rate following myocardial infarction is related to augmented afferent input from the left ventricle.