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.     

Reciprocal and non-reciprocal action of the vagal and sympathetic nerves innervating the heart

Simultaneous recordings were made from vagal and sympathetic fibers innervating the heart in dogs anesthetized with chloralose. Reciprocal relationship between the two autonomic nerves was clearly seen in the baroreceptor reflex. Stimulation of chemoreceptors, however, evoked non-reciprocal responses of the two nerves; at the onset of the chemoreceptor reflex cardiac vagal and sympathetic discharges both increased, then, as baroreceptors became excited due to a pressor response, sympathetic nerve activity suddenly decreased while vagal discharges remained high, indicating the appearance of the reciprocal action typifying the baroreceptor reflex. Decrease in ventilatory volume and a slight increase in end-expired CO2 level augmented greatly both vagal and sympathetic discharges. As the phrenic-locked activity of the two nerves (i.e. the activity in vagus nerve occurs only in the absence of phrenic bursts while sympathetic discharges increase with phrenic bursts) increased, the alternate discharges between the two nerves became more conspicuous and the heart rate fluctuated with the respiratory (phrenic) rhythm. Thus, strong reciprocity between vagus and sympathetic can result in an oscillatory heart rate. When ventilatory volume was increased, both nerve activities decreased below control level. Mild hypoxia had similar effects to hypercapnia though changes in nerve activity were greater. When coactivation of vagal and sympathetic nerve was produced in reflex action, changes in vagal discharges occurred earlier and faster than in the sympathetic fibers. The magnitude of change in vagus activity was also far greater. The elimination of afferents in the vagi, the aortic and sinus nerves reduced cardiac vagal activity greatly. However, discharges were still present and occurred between phrenic bursts, indicating that the vagal "tone" is maintained centrally as well as peripherally by input from receptors in the cardiovascular system. The physiological significance of reciprocal and non-reciprocal control of vagal and sympathetic nerves innervating the heart was discussed.     

Effects of prolactin-releasing peptide microinjection into the ventrolateral medulla on arterial pressure and sympathetic activity in rats

Prolactin-releasing peptide (PrRP), originally isolated from the hypothalamus, is highly localized in the cardiovascular regions of the medulla, and intracerebroventricular administration of PrRP causes a pressor response. In the present study we investigated the cardiovascular effects of PrRP applied to functionally different areas of the ventrolateral medulla (VLM), and to the nucleus tractus solitarius (NTS) and the area postrema (AP). In urethane-anesthetized rats, microinjection of PrRP into the pressor area of the most caudal VLM, recognized as the caudal pressor area in the rat, elicited dose-dependent increases in mean arterial pressure, heart rate, and renal sympathetic nerve activity. In the same injection area, neither thyrotropin-releasing hormone, corticotropin-releasing hormone nor angiotensin II affected these baseline cardiovascular variables. On the other hand, microinjection of PrRP into more rostral parts of the VLM, i.e. the depressor area of the caudal VLM and the pressor area of the rostral VLM, as well as the NTS and the AP, had no effect on these cardiovascular variables. Immunohistochemical analysis in the medulla revealed that the cardiovascularly PrRP-responsive region contained PrRP-immunoreactive cell bodies and nerve fibers. These results suggest that the most caudal VLM is an action site of PrRP to induce a pressor response, which is mediated, at least partly, by the increase in sympathetic outflow.     

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.     

Responses of cardiovascular neurons in the rostral ventrolateral medulla of the normotensive Wistar Kyoto and spontaneously hypertensive rats to iontophoretic application of angiotensin II

In female pentobarbital-anesthetized Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR), changes in spontaneous discharges of cardiovascular neurons in the rostral ventrolateral medulla (RVL) in response to iontophoretic application of angiotensin II (Ang II) were studied and compared. It was found that iontophoretic application of Ang II to RVL increased the spontaneous neuronal activities of 30% of the cardiovascular neurons in both types of rats and that the increase was significantly greater in SHR than in WKY. In both types of rats, there was an increase in arterial blood pressure in response to iontophoretic release of Ang II to RVL. The pressor response was accompanied by tachycardia, which was significantly greater in SHR than in WKY. The present study provides evidence that Ang II acts directly on cardiovascular neurons in RVL, and in SHR, an enhanced sensitivity and responsiveness of the RVL cardiovascular neurons to Ang II may augment the sympathetic outflow from RVL and contribute to the genesis of hypertension.     

Differential effects on sympathetic nerve activities elicited by activation of neurons in the pressor areas of dorsal and rostral ventrolateral medulla in cats.

Changes of the nerve activity of the sympathetic renal and vertebral nerves were elicited by microinjection of sodium glutamate (50 nmol/100 nl) into the pressor areas of the dorsal (DM) and rostral ventrolateral medulla (RVLM) in cats under urethane-chloralose anesthesia. Animals were bilaterally vagotomized, artificially ventilated, and paralyzed with gallamine triethiodide. The vertebral nerve activity always increased when pressor responses were induced by DM or RVLM stimulation. However, the effects of medullary stimulation on the renal nerve activity were variable. Three types of renal nerve responses concomitant with the pressor responses were observed in either baroreceptor-intact or baroreceptor-denervated cats. They were: (1) augmentation (type I); (2) attenuation (type II); and (3) insignificant change (type III). Type I responses were often elicited by RVLM stimulation whereas type II responses were often elicited by DM stimulation. Findings suggested that neurons integrating these sympathetic nerve activities were not equally distributed in the pressor areas of DM and RVLM. This result supports the notion that neurons located in different pressor areas of the brainstem exert differential effects over different sympathetic nerve activities.     

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.     

Effects of drugs on the autonomic control of short-term heart rate variability

The autonomic nervous system links the brain and the heart. Efferent links in the neural control of the heart consist of sympathetic and parasympathetic (vagal) fibers innervating the sinus node. Because sympathetic and vagal firing alter spontaneous sinus node depolarization, cardiac rate and rhythm convey information about autonomic influences on the heart. The easy availability of ECG rendered possible the assessment of sinus rhythm as an index of autonomic outflow. The frequency-domain approach uses non-invasive recordings and appears to provide a quantitative evaluation of the autonomic modulation of cardiovascular function. Spectral profiles resulting from vagal or sympathetic blockades at the cardiac (or vascular) level might be used as references to unravel the mechanism of action of the drug under examination. A more comprehensive assessment will be obtained if spectral analysis is used as a complement to existing techniques applied for describing the neurohumoral status of patients (microneurographic recordings, norepinephrine spillover). This review also reports some pitfalls encountered in variability studies.     

Hepatic portal injection of glucose elevates efferent sympathetic discharges of interscapular brown adipose tissue

Efferent sympathetic discharges of interscapular brown adipose tissue were recorded after three different concentrations of glucose (138, 277, and 416 mM) and 154 mM NaCl were injected into the portal vein or into the right jugular vein. When injected into the portal vein there was a significant increase in the discharge in response to both concentrations of glucose (277 and 416 mM), whereas only 416 mM glucose solution could cause an increase in the discharge when injected into the right jugular vein. There was no appreciable change in the discharge following the NaCl injections into the portal and jugular veins, and the portal glucose responses in the discharge were abolished by transection of the hepatic branch of the vagus nerve. Since stimulated sympathetic activity has been shown to elevate thermogenesis of the adipose tissue, these findings suggest that vagal glucose signals derived from the portal vein may be involved in the regulation of heat production of this tissue.     

The role of vasopressin in the pressor response to bilateral carotid occlusion

Exogenous arginine vasopressin (AVP) has been shown to interact with the arterial baroreflex control of renal sympathetic nerve activity. In addition, we have shown that both AVP and the sympathetic nervous system (SNS) contribute to the pressor response to interruption of cardiopulmonary vagal afferents. This study examined the role and interaction of AVP and the SNS in the pressor response to a reduction of carotid sinus afferent activity by bilateral carotid occlusion (BCO). In addition the role of the area postrema (AP) in mediating the interaction between AVP and the SNS was examined. In aortic denervated conscious dogs, BCO increased mean arterial pressure 51.7 +/- 3.1 mm Hg. Specific vascular (V1) AVP antagonist D(CH2)5Tyr(Me)AVP did not alter the response to BCO (delta 50.8 +/- 7.9 mm Hg). Subsequent ganglionic blockade abolished the response to BCO (delta -10 +/- 3.8). When ganglionic blockade was induced in the absence of AVP antagonist, BCO increased MAP 25.0 +/- 2.8 mm Hg. AVP antagonist following ganglionic blockade eliminated the pressor response to BCO (delta -6.7 +/- 5.1). There was an interaction between AVP and the SNS such that the contribution of one system to the hemodynamic response was greater in the absence of the other system. Ablation of the AP abolished the interaction between reflexly released AVP and the SNS which was observed in intact dogs. These data demonstrate that both AVP and the SNS contribute to the pressor response to BCO. Reflexly released AVP appears to limit the reflex activation of the SNS. The interaction of endogenous AVP and the arterial baroreflex involves the AP. The results are consistent with the hypothesis that vasopressin interacts centrally to limit a reflex increase in sympathetic outflow and thus modulate the pressor response to BCO.     

Long-lasting cardiovascular depression induced by acupuncture-like stimulation of the sciatic nerve in unanaesthetized spontaneously hypertensive rats

The influence of a prolonged low frequency electrical stimulation of the somatic afferents on cardiovascular and sympathetic nerve activities was investigated in unanaesthetized spontaneously hypertensive rats (SHRs) and Wistar-Kyoto normotensive rats (WKRs). In SHR, an elevation of blood pressure, heart rate and splanchnic nerve outflow was elicited during a 30-min period of sciatic nerve stimulation. Following the cessation of the stimulation, depressor response and bradycardia slowly developed and lasted up to 12 h. Activation of the group III or A-delta afferent fibers was essential for this post-stimulatory response. The progressive depressor response and a parallelled reduction of the splanchnic nerve activity, reached their maxima at about 1 h after the termination of the sciatic stimulation. The magnitude of the post-stimulatory depressor response was correlated with the pre-stimulatory control blood pressure level. There were also behavioural changes accompanying the depressor response. The cardiovascular and the behavioural depression were immediately reversed by naloxone (10–15 mg/kg, i.v.). The post-stimulatory depressor response was still present after bilateral sino-aortic denervation, but was absent in animals anaesthetized with chloralose and urethane. Emotional stress prodced by air-blowing on the animal resulted in pressor response and tachycardia during the period of the stressful stimulation, but there was no depressor response following the termination of air-blowing. These findings indicate a sympathetic and cardiovascular depression induced by a prolonged stimulation of the somatic group III or A-delta afferent fibers; its long duration and naloxone reversibility suggest the involvement of endorphins in the mechanism of this response. The physiological significance of the effects of the prolonged somatic afferent stimulation and its possible relations with acupuncture are discussed.     

The effect of electro-acupuncture stimulation on the muscle blood flow of the hindlimb in anesthetized rats

The effect of electro-acupuncture stimulation (EAS) on blood flow in the muscle biceps femoris (MBF) and on mean arterial pressure (MAP) was investigated in anesthetized, artificially ventilated rats. EAS was applied to a hindpaw for 30 s at intensities of 0.1-10.0 mA and at frequencies of 1-20 Hz, and MBF was measured by laser Doppler flowmetry. EAS at less than 1.0 mA, which excited group II fibers maximally and III fibers partially in a saphenous nerve, had no significant effect on MBF or MAP, although both revealed variable responses. EAS at 1.5 mA, which additionally excited group III fibers almost maximally and was subthreshold for group IV fibers, produced a small but significant increase in MBF and MAP. These responses were further increased at 2.0 mA or more, which was suprathreshold for group IV fibers. The increased response of MBF at 10.0 mA was followed by a small decrease in MBF. EAS at 1.5 mA or more also elicited a decrease in renal blood flow (RBF) and an arterial pressor response. Following severance of the bilateral splanchnic nerves, EAS at 10.0 mA induced only a slight increase in MAP and a decrease in MBF. The decrease in MBF was abolished following further severance of the bilateral lumbar sympathetic trunks (LSTs). In conclusion, EAS to a hindpaw at a stimulus strength sufficient to excite group III and IV afferent fibers, particularly group IV afferent fibers, can produce a reflex decrease in MBF via a reflex activation of muscle sympathetic activity, although this decrease in MBF is overridden by an increase in MBF caused passively by a reflex MAP pressor response elicited by a reflex increase, at least in splanchnic sympathetic activity.     

Role of peripheral and central catecholaminergic and cholinergic mechanisms in the cardiovascular effects of thyrotropin-releasing hormone

The mechanisms of the cardiovascular effects of i.c.v. administered thyrotropin-releasing hormone (TRH) were studied in anesthetized rats. The pressor response to TRH was blocked after depletion of catecholamines by i.p. reserpine whereas vagotomy or i.v. methylatropine reduced the TRH-induced tachycardia. Centrally administered catecholaminergic or cholinergic receptor antagonists failed to block the cardiovascular effects of TRH. However, centrally administered reserpine reduced the pressor response to TRH and the affinity of its specific binding in brain homogenates. Similar reduction in the affinity of TRH binding was observed after depletion of brain serotonin with p-chlorophenylalanine (PCPA), which was earlier shown to antagonize the TRH-induced pressor effect. It was concluded that TRH acts through a central mechanism to enhance the sympathetic outflow and to attenuate the vagal cardiac activity which leads to hypertension and tachycardia. Central serotonergic mechanisms rather than those related to catecholamines appear to be involved in the pressor response to TRH.     

Cardiovascular responses to electrical stimulation of sympathetic nerves in the pithed mouse

The pithed rat model has been used extensively to study peripheral cardiovascular responses to electrical stimulation of the sympathetic nervous system, as pithing eliminates central and reflex effects. However, since the transgenic mouse has become a standard and economical model organism, an electrically stimulated pithed mouse would facilitate a variety of studies. We have developed surgical techniques, drug doses and stimulation parameters for an electrically stimulated pithed mouse to study peripheral sympathetic nerve effects on blood pressure. Similar to the pithed rat, the pithed mouse showed voltage and frequency-dependent blood pressure responses to a pulsed train of electrical stimuli. In addition, alpha-adrenergic stimulation with phenylephrine gave a marked systolic pressor response, while the beta2 agonist salbutamol lowered diastolic blood pressure. Furthermore, pithed transgenic mice unable to synthesize catecholamines in adrenergic cells displayed smaller pressor responses than pithed control mice. In summary, the electrically stimulated pithed mouse can be used to study peripheral effects of the sympathetic system on cardiovascular dynamics unencumbered by central responses.     

Central alpha-melanocyte-stimulating hormone acts at melanocortin-4 receptor to activate sympathetic nervous system in conscious rabbits

Intracerebroventricular injection of alpha-melanocyte-stimulating hormone (alpha-MSH) elicited increases in arterial pressure and renal sympathetic nerve activity in conscious rabbits. Pretreatment with intracerebroventricular injection of agouti-related protein, an endogenous melanocortin-3 and 4 receptor antagonist, prevented cardiovascular and sympathetic responses to alpha-MSH. Pretreatment with intracerebroventricular injection of JKC-363, a synthetic specific melanocortin-4 receptor antagonist, also prevented cardiovascular and sympathetic responses to alpha-MSH. In contrast, intravenous alpha-MSH (1 nmol) failed to cause any cardiovascular responses. These results suggest that intracerebroventricularly administered alpha-MSH acts at the melanocortin-4 receptor in the brain and activates sympathetic outflow, resulting in an increase in arterial pressure.     

The involvement of the sympathetic nervous system in the centrogenic pressor and tachycardiac effects of prostaglandins E2 and F2 alpha in anaesthetised cats

The intracerebroventricular (i.c.v.) administration of prostaglandin E2 (PGE2, 1 micrograms) and prostaglandin F2 alpha (PGF2 alpha, 10 micrograms) produced prolonged pressor and tachycardiac responses in chloralose-anaesthetised cats. Phenoxybenzamine-pretreatment completely prevented the pressor response without altering the tachycardiac response, whereas propranolol intervention completely inhibited the tachycardiac response and also attenuated the pressor response. The pretreatment with pentolinium completely antagonised both the pressor and tachycardiac responses to i.c.v. PGE2 and PGF2 alpha. The results suggest that the centrally administered PGE2 and PGF2 alpha augment sympathetic outflow to the heart and vascular system and thereby cause excitatory cardiovascular responses in anaesthetised cats.     

Reversible vagal blockade in conscious rats using a targeted delivery device

Reversible methods of nerve blockade greatly aid neurophysiological and behavioral studies. We have developed an implantable device for the local delivery of anesthetics to the area surrounding the vagal nerve in rats. The device consists of a thick silicone tube for insulating the nerves from the surrounding tissue, and a thin silicone tube for the infusion of anesthetics into the insulating tube. The in vivo performance of the device was tested electrophysiologically, and cardiovascular responses to vagal stimulation were measured in conscious animals. Nerve conductivity was completely blocked by injection of a small amount (<20 microl) of 1% lidocaine, with conductivity subsequently recovering gradually after 10-40 min. Electrical stimulation of the right vagus nerve in conscious rats increased arterial pressure while decreasing heart rate. The local blockade of afferent fibers abolished the arterial pressure response but preserved the bradycardic response to vagal nerve stimulation. The targeted delivery device was useful for reversible vagal blockade in conscious rats.     

Arterial hypertension elicited either by lesions or by electrical stimulations of the rostral hypothalamus in the rat

Bilateral anodal lesions performed with stainless steel electrodes placed either in the anterior medial (AMH) or lateral (ALH) hypothalamus, or in the ventromedial nucleus (VMH), induced in unrestrained rats the rapid development of arterial hypertension, tachycardia and death. Similarly placed cathodal lesions performed with platinum electrodes failed to elicit the cardiovascular syndrome. The electrical stimulation of the AMH, ALH or VMH caused an increase in the arterial blood pressure in anesthetized rats. This pressor response was characteristically biphasic and consisted of a sharp increase in arterial pressure at the onset of the stimulation, followed by a second elevation at the end of the stimulation. The hypertension evoked either by lesions or by stimulations of the hypothalamus, appeared to depend largely on a neurally mediated release of adrenal medullary catecholamines, and to some extent on the activation of the sympathetic vasoconstrictor fibers. Bilateral adrenalectomy, or adrenal demedullation, prevented the hypertension evoked by lesions, and selectively blocked the important secondary phase of the pressor response elicited by stimulation, but did not affect the primary phase. The latter was specifically eliminated by the destruction of the sympathetic vasomotor axons with 6-hydroxydopamine (6-OHDA). On the other hand, the tachycardia evoked by lesions or stimulations of the medial hypothalamus, resulted from an increase in sympathetic neural discharges to the heart, and it was abolished either by β-receptor blockade with sotalol or by chemical sympathectomy with 6-OHDA. In contrast, the tachycardia occurring after lesions of the lateral hypothalamus was entirely due to circulating adrenal medullary catecholamines and it was eliminated by adrenalectomy. It is concluded that acute hypertension and tachycardia produced by anodal lesions performed with stainless steel electrodes results from the excitation of the hypothalamus, possibly due to the irritative action of the metallic ions deposited at the lesion sites. The observations of cardiovascular responses entirely due to adrenomedullary secretions suggests that the control of the adrenal medulla is at least partially distinct from that of the sympathetic vasoconstrictor and cardiac fibers, at the rostral hypothalamic level.     

Differential control of sympathetic activity to kidney and skeletal muscle by ventral medullary neurons.

A rise in arterial blood pressure can be evoked by microinjections of D,L-homocysteic acid into localized regions of the ventrolateral medulla of the cat. Three patterns of sympathetic discharge can be identified during the pressor response. A differential pattern consisting of an increase in renal nerve activity and no change in sympathetic activity to skeletal muscle vasculature can be elicited from sites ventromedial to the caudal pole of the facial nucleus. From more lateral and caudal sites, a generalized sympatho-excitation is evoked in the outflow to both the kidney and hindlimb muscle vasculature. A third response consisting of a differential increase in muscle sympathetic activity simultaneous with a small decrease in renal nerve activity could be evoked from caudal sites, lateral to the inferior olives and superficial to the ventral surface. The results show that ventral medullary neurons can selectively activate sympathetic outflow to control specific vascular beds. These data may support the hypothesis that the ventrolateral medulla contains discrete groups of topographically arranged neurons that can differentially control sympathetic tone to various end-organs.     

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.