Sympathetic Efferent Discharge Research Articles

Mechanisms Contributing to the Generation of Mayer Waves.

Mayer waves may synchronize overlapping propriobulbar interneuronal microcircuits constituting the respiratory rhythm and pattern generator, sympathetic oscillators, and cardiac vagal preganglionic neurons. Initially described by Sir Sigmund Mayer in the year 1876 in the arterial pressure waveform of anesthetized rabbits, authors have since extensively observed these oscillations in recordings of hemodynamic variables, including arterial pressure waveform, peripheral resistance, and blood flow. Authors would later reveal the presence of these oscillations in sympathetic neural efferent discharge and brainstem and spinal zones corresponding with sympathetic oscillators. Mayer wave central tendency proves highly consistent within, though the specific frequency band varies extensively across, species. Striking resemblance of the Mayer wave central tendency to the species-specific baroreflex resonant frequency has led the majority of investigators to comfortably presume, and generate computational models premised upon, a baroreflex origin of these oscillations. Empirical interrogation of this conjecture has generated variable results and derivative interpretations. Sinoaortic denervation and effector sympathectomy variably reduces or abolishes spectral power contained within the Mayer wave frequency band. Refractorines of Mayer wave generation to barodeafferentation lends credence to the hypothesis these waves are chiefly generated by brainstem propriobulbar and spinal cord propriospinal interneuronal microcircuit oscillators and likely modulated by the baroreflex. The presence of these waves in unitary discharge of medullary lateral tegmental field and rostral ventrolateral medullary neurons (contemporaneously exhibiting fast sympathetic rhythms [2–6 and 10 Hz bands]) in spectral variability in vagotomized pentobarbital-anesthetized and unanesthetized midcollicular (i.e., intercollicular) decerebrate cats supports genesis of Mayer waves by supraspinal sympathetic microcircuit oscillators. Persistence of these waves following high cervical transection in vagotomized unanesthetized midcollicular decerebrate cats would seem to suggest spinal sympathetic microcircuit oscillators generate these waves. The widespread presence of Mayer waves in brainstem sympathetic-related and non-sympathetic-related cells would seem to betray a general tendency of neurons to oscillate at this frequency. We have thus presented an extensive and, hopefully cohesive, discourse evaluating, and evolving the interpretive consideration of, evidence seeking to illumine our understanding of origins of, and insight into mechanisms contributing to, the genesis of Mayer waves. We have predicated our arguments and conjectures in the substance and matter of empirical data, though we have occasionally waxed philosophical beyond these traditional confines in suggesting interpretations exceeding these limits. We believe our synthesis and interpretation of the relevant literature will fruitfully inspire future studies from the perspective of a more intimate appreciation and conceptualization of network mechanisms generating oscillatory variability in neuronal and neural outputs. Our evaluation of Mayer waves informs a novel set of disciplines we term quantum neurophysics extendable to describing subatomic reality. Beyond informing our appreciation of mechanisms generating sympathetic oscillations, Mayer waves may constitute an intrinsic property of neurons extant throughout the cerebrum, brainstem, and spinal cord or reflect an emergent property of interactions between arteriogenic and neuronal oscillations.

Blood pressure long term regulation: A neural network model of the set point development

BackgroundThe notion of the nucleus tractus solitarius (NTS) as a comparator evaluating the error signal between its rostral neural structures (RNS) and the cardiovascular receptor afferents into it has been recently presented. From this perspective, stress can cause hypertension via set point changes, so offering an answer to an old question. Even though the local blood flow to tissues is influenced by circulating vasoactive hormones and also by local factors, there is yet significant sympathetic control. It is well established that the state of maturation of sympathetic innervation of blood vessels at birth varies across animal species and it takes place mostly during the postnatal period. During ontogeny, chemoreceptors are functional; they discharge when the partial pressures of oxygen and carbon dioxide in the arterial blood are not normal.MethodsThe model is a simple biological plausible adaptative neural network to simulate the development of the sympathetic nervous control. It is hypothesized that during ontogeny, from the RNS afferents to the NTS, the optimal level of each sympathetic efferent discharge is learned through the chemoreceptors' feedback. Its mean discharge leads to normal oxygen and carbon dioxide levels in each tissue. Thus, the sympathetic efferent discharge sets at the optimal level if, despite maximal drift, the local blood flow is compensated for by autoregulation. Such optimal level produces minimum chemoreceptor output, which must be maintained by the nervous system. Since blood flow is controlled by arterial blood pressure, the long-term mean level is stabilized to regulate oxygen and carbon dioxide levels. After development, the cardiopulmonary reflexes play an important role in controlling efferent sympathetic nerve activity to the kidneys and modulating sodium and water excretion.ResultsStarting from fixed RNS afferents to the NTS and random synaptic weight values, the sympathetic efferents converged to the optimal values. When learning was completed, the output from the chemoreceptors became zero because the sympathetic efferents led to normal partial pressures of oxygen and carbon dioxide.ConclusionsWe introduce here a simple simulating computational theory to study, from a neurophysiologic point of view, the sympathetic development of cardiovascular regulation due to feedback signals sent off by cardiovascular receptors. The model simulates, too, how the NTS, as emergent property, acts as a comparator and how its rostral afferents behave as set point.

Cardiac vagal and sympathetic efferent discharges are differentially modified by stretch of skeletal muscle.

We directly measured cardiac vagal efferent nerve activity (CVNA) and cardiac sympathetic efferent nerve activity (CSNA) in cats decerebrated at the level of the precollicular-premammillary body while the hindlimb or the triceps surae muscle was passively stretched. CVNA gradually decreased during passive stretch of the hindlimb, and this decrease was sustained throughout the stretch. CSNA increased at the onset of passive stretch, but this increase was not sustained. CVNA and CSNA responded differentially to graded passive stretches of the triceps surae muscle as well as the hindlimb. The sustained decrease in CVNA but not the initial increase in CSNA became greater depending on muscle length and developed tension. The time course and direction of the cardiac autonomic responses to muscle stretch were not affected by partial sinoaortic denervation, although the magnitude of the CSNA response was augmented. We conclude that the muscle mechanoreflex contributes to differential regulation of cardiac parasympathetic and sympathetic efferent discharges during passive stretch of skeletal muscle irrespective of arterial baroreceptor input.

Leptin effects on feeding-related hypothalamic and peripheral neuronal activities in normal and obese rats

We investigated the effects of leptin on central and/or peripheral feeding-related neuronal networks in Wistar male rats either normal (350–450 g) or Zucker obese (500–800 g). Low doses (1–10 pg) of leptin inhibited glucose-sensitive vagal hepatic afferent discharges and facilitated sympathetic efferent discharges to brown and white adipose tissue. Most (40–75%) neurons in the arcuate nucleus were significantly inhibited by superperfusion with leptin (0.1 nM–10 pM) under in vitro conditions. In anesthetized animals, leptin was applied electrophoretically to single hypothalamic neurons. Both glucose-sensitive neurons (GSNs) and non-GSNs in the feeding center (LHA) were significantly inhibited. Most glucoreceptor neurons in the satiety center (VMH) were significantly excited. Their depolarization was confirmed by activation of Na + and K + channels by 10 −11 M leptin using the perforate blind patch-clamp method. Although leptin excited GSNs in the parvocellular part of the paraventricular nucleus, the effects of leptin on such neuronal activity were slight or absent in Zucker obese rats. These results suggest that the feeding-suppression effects of leptin are mediated by its effects on signal transduction through both the central and the peripheral nervous systems.

Synchronization of somato-sympathetic outflows during exercise: role for a spinal rhythm generator.

The synchronization of somatic motor outflow and sympathetic efferent activity during exercise has important functional consequences. For example, a certain degree of sympathetic vasoconstriction to active skeletal muscle vascular beds may be required to prevent an excessive decrease in vascular resistance during intense dynamic exercise involving a large skeletal muscle mass. Moreover, the redistribution of blood flow away from non-exercising vascular beds to contracting skeletal muscles is necessary to meet their increased metabolic demands. Historically, the nervous system has been separated arbitrarily into a volitional (somatic) and a reflex (autonomic) control system that does not necessitate volitional input (Koizumi & Brooks, 1972). However, during exercise this partition of the somatic and autonomic control systems is replaced by an overlapping control system that influences both somatic and sympathetic outflows in a parallel fashion. Previous work has suggested that the integration and co-ordination of the somatic and sympathetic motor responses during exercise were mediated by a supraspinal neural mechanism referred to as central command (Waldrop et al. 1996). However, there is an accumulating body of evidence, including papers on the role of the spinal cord in the regulation of sympathetic outflow (Weaver & Stein, 1989), suggesting that rhythmic neural activity destined for somatomotor and sympathetic outflows may be under the control of intrinsic neuronal circuitry in the spinal cord. In this issue of The Journal of Physiology, the paper by Chizh et al. (1998) demonstrates for the first time that some components of somatic motor and sympathetic neural outflows are synchronized by a spinal mechanism. The authors studied the relationship between sympathetic and somatic motor outflows from the thoraco-sacral spinal cord using an isolated trunk-hindquarters preparation of the adult mouse. They found that some of the activity in both somatic and sympathetic outflows was coupled. However, since there was also sympathetic neural activity that showed burst discharges in the absence of somatic motor activity, the spinal mechanism responsible for generating sympathetic burst activity was not the same mechanism that was responsible for somato-sympathetic coupling. Therefore, there remained spinal mechanisms that were capable of generating bursting activity independently of somatic and sympathetic activities. When NMDA was added to the perfusate to induce rhythmic somatic motor activity, a dose-dependent bursting pattern in sympathetic efferent and somatic motor nerves was evoked that was coupled at similar frequencies. Correlational analyses found a strong coherence between somatic motor outflow and sympathetic efferent discharge when triggered from peaks in somatic motor activity. However, this synchronization was not found when triggered from the peaks of sympathetic discharge. This finding led Chizh et al. (1998) to hypothesize that the generating mechanism responsible for somatic locomotor activity was the same mechanism responsible for coupling somatic outflow to sympathetic activity. These findings support the notion that the spinal cord possesses the necessary neuronal ‘machinery’ for generating and coupling sympathetic discharge with somatic motor outflow independently of supraspinal structures (i.e. the spinal rhythm generator represents a spinal central command). Important adjustments occur in the heart and blood vessels during exercise in order to provide the appropriate oxygen delivery to match the metabolic demand of contracting skeletal muscle. The coupling of somatic motor and sympathetic outflows is mediated by supraspinal neural mechanisms (supraspinal central command) in humans and animals (Fig. 1). In humans, intense intermittent static exercise produced a one-to-one synchronization of somatic motor activity with muscle sympathetic nerve activity that was purportedly directed to skeletal muscle vasculature (Victor et al. 1995). This synchronization persisted in the presence of both partial neuromuscular blockade (i.e. to increase central command) and after local anaesthetic block of the arm nerves to eliminate afferent feedback from skeletal muscle. Likewise, electrical and chemical stimulation of the hypothalamic locomotor region in decorticate cats after neuromuscular blockade evokes fictive locomotion that produces increases in arterial blood pressure (Waldrop et al. 1996) and synchronization of sympathetic nerve activity with hindlimb motor nerve activity (Hajduczok et al. 1991). And, as seen in humans, the synchronization of somatic motor activity and sympathetic discharge was unaffected by peripheral feedback mechanisms. These findings suggest that central command signals of supraspinal origin can regulate and co-ordinate sympathetic and somatomotor outflows during exercise. Figure 1 Synchronization of somatic motor outflow and sympathetic efferent activity during exercise is mediated by supraspinal and spinal mechanisms. The important work of Chizh et al. (1998) extends our understanding of the synchronization of somatic motor activity and sympathetic outflow by highlighting the role of a spinal somato-sympathetic generator (Fig. 1). Also, the coupling of somato-sympathetic neural outflows in the spinal cord may represent an exquisite mechanism to finely tune sympathetic discharge to the segmental level of somatic motor outflow during exercise. Finally, {fontsize the degree to which supraspinal central command signals influence the somato-sympathetic spinal generator needs to be studied to further our understanding of somato-sympathetic coupling during volitional exercise.

Vasopressin receptors in the area postrema differentially modulate baroreceptor responses in rats

This study examined the effects of microinjection of [Arg 8]vasopressin (AVP) into the area postrema (AP) on baroreceptor reflex control of heart rate (HR) and sympathetic efferent discharge (SED) in anesthetized rats. Comparable increments in blood pressure evoked by systemic AVP, as opposed to phenylephrine, were associated with significantly greater reflex bradycardia. Similarly, AVP augmented the baroreflex-mediated sympathoinhibition; however, this effect was evident only with the lower increments in arterial pressure (< 45 mm Hg) i.e. following systemic administration of small doses of AVP. Beyond 45 mm Hg there was no further augmentation of baroreflex-mediated sympathoinhibition showing the non-linearity of the response compared to phenylephrine which was linear over a wide range of induced pressure increases. Microinjection of AVP into the AP produced a differential effect on HR and SED responses to baroreceptor activation by systemically administered phenylephrine, the baroreflex slope of HR response was attenuated whereas that of SED was enhanced. Microinjection of the V 1 antagonist AVPX (d(CH 2)5Tyr(Me)-AVP) into the AP abolished the inhibitory effect of AVP on the baroreceptor-HR response suggesting that V, receptors are involved in this response. Further, AVPX inhibited the baroreceptor-SED response suggesting that V, receptors in the AP are tonically involved in modulating the baroreceptor reflex control of SED. Qualitatively similar but smaller responses were obtained following microinjection of AVP into the nucleus tractus solitarii (NTS) suggesting involvement of neural input from the AP to the NTS in AVP-evoked responses in the AP. It is concluded that the AVP receptors in the AP differentially modulates the baroreceptor reflex control of HR and SED.

Spectral analysis of sympathetic discharge in decerebrate cats

To evaluate if the 0.1-Hz low-frequency oscillations of R-R interval are a reflection of a rhythmical pattern of discharge of the sympathetic outflow, we analysed in 10 decerebrate cats heart rate and cardiac sympathetic efferent discharge variability. A predominant low-frequency component was present in both signals, thus suggesting that the 0.1-Hz rhythm indeed reflects a rhythmical pattern of discharge of sympathetic outflow.

Selective sensitization by l-glutamate of baroreflex-mediated bradycardia following microinjection into the rostral ventrolateral medulla

This study examined the role of l-glutamate receptors in different sites in the rostral ventrolateral medulla (RVL) on baseline mean arterial pressure (MAP), heart rate (HR), sympathetic efferent discharge (SED) as well as baroreflex control of HR and SED. Depending on the site, the hemodynamic responses varied from an increase to a decrease in MAP which was accompanied by a similar or an opposite change in HR; the change in SED correlated positively with the change in MAP. Because injection of the test dose of glutamate (5 nM) into the deepest portion of the RVL produced the most pronounced increases in MAP, which was accompanied by a brisk bradycardia, we decided to investigate the nature of these responses. Dose-related sympathoexcitatory, pressor and bradycardic effects were obtained in response to 1, 3, 5 and 10 nM glutamate. The glutamate antagonist, glutamate diethylester (GDEE) abolished these responses and decreased baseline MAP, HR and SED. That glutamate-evoked bradycardia was baroreceptor-mediated was supported by: (1) the bradycardia was not only eliminated but was also converted to a small but significant tachycardic response in sinoaortic denervated rats and following cardiac muscarinic blockade; (2) glutamate substantially sensitized the baroreceptor HR and had no effect on SED response when tested by phenylephrine; and (3) GDEE abolished the sensitizing action of glutamate on the baroreflex control of HR. We conclude that glutamatergic pathways in the deepest portion of the RVL are tonically active and subserve sympathoexcitatory, pressor and tachycardic effects. Also, glutamate differentially sensitizes the baroreceptor reflex pathways that control HR by mainly activating the vagal component of the reflex, an effect which masks its tachycardic effect.

Capsaicin‐sensitive afferents activate a sympathetic intestinointestinal inhibitory reflex in dogs.

1. In urethane-anaesthetized dogs, an intra-arterial infusion of capsaicin (0.7-14 nmol min-1) into a separated jejunal segment inhibited a vagally evoked cholinergic contraction of the other non-infused segments. The mechanism of this reflex was investigated. 2. The inhibition by capsaicin was abolished after bilateral splanchnic nerve section or cervical spinal cord transection (C5 or C6), but was unaffected by bilateral vagotomy. Decerebration partially reduced the inhibition. 3. The inhibition by capsaicin was abolished by pre-treatment with phentolamine or yohimbine, but was unaffected by prazosin or propranolol. 4. Sympathetic efferent discharge of the mesenteric nerve increased with capsaicin application, during which time vagally evoked contractions were inhibited. 5. Single-unit discharges of the major splanchnic and mesenteric afferents increased with capsaicin infusion to the loop which was innervated by the units. 6. Together the results implied that capsaicin stimulated canine intestinal primary afferents, resulting in the sympathetic intestinointestinal inhibitory reflex supraspinally. The inhibition of vagally evoked contractions may be due to a presynaptic inhibition via alpha 2-adrenoceptors, which are activated by the reflex.

Impairment of baroreceptor reflex control of heart rate but not sympathetic efferent discharge by central neuroadministration of ethanol.

We investigated the acute hemodynamic effects of ethanol microinjection into brain areas known to influence cardiovascular function and reflexes. In chloralose-anesthetized rats, ethanol had no effect on baseline mean arterial pressure, heart rate, or sympathetic efferent discharge when microinjected into the nucleus tractus solitarius, the dorsal motor nucleus of the vagus, the rostral ventrolateral medulla, or the posterior hypothalamus. On the other hand, ethanol microinjection into the anterior hypothalamus caused a site-dependent pressor effect and an increase in sympathetic efferent discharge. Baroreceptor heart rate response but not sympathetic efferent discharge response was impaired by ethanol microinjection into the nucleus tractus solitarius, the dorsal motor nucleus of the vagus, and the rostral ventrolateral medulla, suggesting that ethanol involves one or more of these areas in its inhibitory effect on baroreceptor heart rate response and that ethanol has a selective action on baroreceptor reflex control of heart rate. The findings that 1) the effect was dose dependent and 2) injection of ethanol outside of, or an equal volume of cerebrospinal fluid into, the nucleus tractus solitarius had no effect on the response strongly suggest that the observed effect on baroreceptor heart rate response was ethanol mediated. Ethanol microinjection into the dorsal motor nucleus of the vagus impaired the heart rate response, thus raising the possibility that leakage of ethanol to that area from the nucleus tractus solitarius might have contributed to its effect. These findings show that ethanol has a pressor and sympathoexcitatory site of action within the anterior hypothalamus and that it selectively impairs baroreceptor heart rate response via a central site of action; the mechanisms by which ethanol produces these effects remain to be elucidated.

12 Water disturbances in cardiac failure

The non-osmotic stimulation of release of arginine vasopressin (AVP) seems to be the main determinant of the impaired water excretion and hyponatraemia in patients with cardiac failure. This non-osmotic stimulation of AVP release could be secondary to a decrease in stroke volume to which the ventricular receptors respond by decreasing the vagal afferent input to the hypothalamus via the mid-brain. Improvement of cardiac stroke volume would then decrease AVP release and improve water excretion. In cardiac failure, the non-osmotic stimulation of AVP release is not clearly modulated by the renin-angiotensin system or by the atrial natriuretic peptide plasma concentration. Nevertheless, physiological concentrations of atrial natriuretic peptide could inhibit the renal epithelial water transport at the collecting duct level. Water-loading and osmotic-loading experiments in patients with cardiac failure indicated that the release of AVP is still under osmotic control and favoured the concept that volume depletion in general and cardiac failure in particular may lower the osmotic threshold and increase the osmotic sensitivity to vasopressin release. Experiments using a specific vasopressin antagonist rarely indicated a vasoconstrictor role for endogenous AVP in either experimental or clinical cardiac failure. Intrarenal factors also contributed to the impaired water excretion observed in patients with cardiac failure: increased central sympathetic efferent discharge and stimulation of the renin-angiotensin-aldosterone system would be expected as a consequence of the decreased effective arterial blood volume. These effects could then decrease maximal reabsorption of solute further impairing the ability of the kidney to excrete free water. The impaired water excretion is correlated with the severity of the cardiac deterioration and thus has prognostic implications.

Impairment of central mediation of the arterial baroreflex by acute ethanol administration

We investigated the possibility that the impairment of baroreflex control of heart rate was due to an action of ethanol on the central component of the baroreflex arc. Baroreceptors and baroreceptor afferents were removed from the arc by sino-aortic denervation and the central end of the left aortic depressor nerve was stimulated. Stimulation frequency response curves relating the decreases in blood pressure, heart rate and sympathetic efferent nerve discharge to the frequency of stimulation were constructed before and after the administration of 0.33, 0.66 and 1 g/kg of ethanol administered systemically. Except for a small decrease in blood pressure following the 1 g/kg dose, ethanol administration did not produce any change in baseline heart rate or blood pressure but the frequency response curve of heart rate was reset by the two lower doses of ethanol whereas the dose of 1 g/kg produced frank impairment of baroreflex control. Similarly the dose of 1 g/kg also impaired the depressor response to aortic nerve stimulation whereas it did not impair the baroreflex control of sympathetic efferent discharge. These data suggest a differential effect of ethanol on central pathways that control baroreflex responses. To ensure that the effect of ethanol was not due to an action of ethanol on an end organ, the heart, a separate group of rats were prepared with sino-aortic denervation and the peripheral end of the cut right vagus nerve was stimulated with increasing frequency. Ethanol did not affect the response to stimulation of the vagus nerve showing that the impairment of baroreflex control of cardiovascular variables was primarily of central origin.

Inotropic responses of the left ventricle to changes in heart rate in anesthetized rabbits.

Factors known to influence left ventricular contractility include preload, afterload, circulating catecholamine concentration, efferent sympathetic discharge, and heart rate. Heart rate influences have been primarily determined in the dog, whereas the influence of heart rate in smaller mammals has not been determined. Eight pentobarbital-anesthetized rabbits were instrumented to measure electrocardiogram, heart rate, left ventricular pressure, end-diastolic pressure, dP/dt, and mean and pulsatile aortic pressures. Systematic bradycardia was induced by stimulating the peripheral end of the sectioned right vagus nerve. Between 293 and 235 beats/min, there was no change in (dP/dt)max as heart rate was decreased. Below this range there was a direct relationship between (dP/dt)max and heart rate. Preload remained unchanged down to 132 beats/min. There was a small but significant decrease in afterload (0.09 mmHg X beat-1 X min-1; 1 mmHg = 133.32 Pa) throughout the decrease in heart rate. Infusion of propranolol (2.0 mg/kg) produced no marked change in the heart rate - (dP/dt)max relationship, although both resting heart rate and (dP/dt)max were reduced. This study demonstrates that (dP/dt)max is not influenced by changes in heart rate above 235 beats/min in the pentobarbital-anesthetized rabbit. These results differ from findings in other animals, and demonstrate that species and heart rate ranges must be considered when drawing conclusions regarding (dP/dt)max as a reliable index of contractility.

α2-adrenoceptor-mediated coronary vasoconstriction persists after exhaustion of coronary dilator reserve

The effect of intracoronary administration of the selective α 2-adrenoceptor agonist B-HT 920 on coronary resistance was tested in 14 open-chest dogs before and after exhaustion of coronary dilator reserve. Under both conditions B-HT 920 increased coronary resistance to the same extent: 27 ± 4% before and 32 ± 3% after. Administration of B-HT 920 did not affect cardiovascular haemodynamics significantly, although after exhaustion of coronary dilator reserve left ventricular dP dt max decreased slightly by 12 ± 5%. While efferent cardiac sympathetic discharge remained constant during control conditions it increased by 27 ± 7% when B-HT 920 was administered into a stenotic coronary artery. We conclude that, in contrast to observations made on α 1-adrenoceptors, activation of coronary α 2-adrenoceptors may have deleterious effects after exhaustion of coronary dilator reserve because these receptors mediate a comparable constriction in well- and under-perfused coronary vessels. Thus they are unlikely to favour a redistribution of coronary blood flow into under-perfused myocardial regions. In addition, this unfavourable effect of B-HT 920 on coronary perfusion after coronary dilator reserve has been exhausted may be further exacerbated by an increase in efferent sympathetic discharge.

Inhibitory effects on fast sympathetic rhythms

In decerebrate cats, the effects of barbiturate anesthesia and of pulmonary afferent activity (produced by lung inflation) on fast (ca. 10/s) rhythms in sympathetic efferent discharges (cervical sympathetic and splanchnic) were analyzed. These inhibitory influences, in addition to reducing overall activity, eliminated or drastically reduced the highest frequency oscillations. Barbiturate anesthesia also markedly reduced high frequency oscillations (ca. 100/s) in phrenic discharge. Apparently, then, the occurrence of fast neural rhythms is dependent on the level of tonic excitatory activity.

Reflex modulation of carotid sinus baroreceptor activity in the dog.

Carotid sinus baroreceptor (CBR) sensitivity may be increased by electrical stimulation of sympathetic nerves passing to the carotid sinus region. It remains unknown if reflexly induced changes in efferent sympathetic discharge affect CBR function. In 17 anesthetized dogs, we reflexly induced alterations in sympathetic discharge and recorded CBR activity originating from a vascularly isolated carotid sinus. The stimulus to the baroreceptors was pulsatile with constant mean and pulse pressure. Occlusion of the contralateral common carotid artery (n = 6) resulted in a reflex increase in arterial pressure (116 +/- 10 to 153 +/- 14 mmHg) and an increase (121 +/- 2% of control) in baroreceptor activity (P less than 0.05). Inferior vena caval occlusion (n = 6), which induced a reduction in arterial pressure (145 +/- 19 to 75 +/- 21 mmHg), also provoked an increase (141 +/- 10% of control) in baroreceptor discharge (P less than 0.05). Raising pressure (to 200 mmHg) in the contralateral carotid sinus (n = 7) resulted in a reflex decrease in arterial pressure (169 +/- 16 to 129 +/- 13 mmHg) and a reduction (82 +/- 3% of control) in baroreceptor activity (P less than 0.05). The changes in baroreceptor discharge were abolished by ipsilateral cervical sympathectomy or ganglionic blockade (n = 4). Our findings demonstrate that reflexly induced alterations in the activity of sympathetic fibers innervating the carotid sinuses can modulate baroreceptor discharge.

Nerve pathophysiology and mechanisms of pain in causalgia

In contrast to sensory endings in skin, muscle, etc., afferents in the mid-course of intact nerves are normally incapable of generating impulses upon slow or prolonged depolarization. However, after various types of nerve injury, including complete nerve section and local demyelination, an ectopic pacemaker capability develops. One peculiarity of such abnormally differentiated sites is chemosensitivity to α-adrenergic agonists and to sympathetic efferent discharge. Such ectopic chemosensitivity may well be involved in the etiology of paraesthesias and pain in reflex sympathetic dystrophies including causalgia. Specifically, it is proposed that the fundamental cause of these conditions is the development of abnormal electrogenic membrane properties in the region of demyelination and sprout outgrowth. These abnormal properties presumably include the appearance of excess inward current conductances and ectopic α-adrenergic receptors. Catecholamines released from sympathetic efferents in the area of injury locally depolarize damaged sensory fibers, and because of the abnormal electrogenic properties of these fibers, an abnormal afferent discharge is generated.

The effect of atenolol on the spontaneous and reflex activity of the sympathetic nerves in the cat: influence of cardiopulmonary receptors.

1 Atenolol reduces sympathetic efferent discharge and attenuates the responses of the sympathetic nerves to changes in blood pressure. The present experiments were carried out to determine whether these changes were mediated by cardiopulmonary receptors whose afferents lie in the vagal nerves.2 Cats were anaesthetized with alpha-chloralose and artificially ventilated. In one group of cats recordings were made of sympathetic efferent discharge from few-fibre preparations from the lumbar trunk, splanchnic or renal nerves over a range of blood pressures. In a second group of cats changes in heart rate and blood pressure in response to bilateral occlusion of the common carotid arteries were investigated. In all cats the influence of vagal afferent fibres was removed by cooling both vagal nerves in the neck, both before and after administration of atenolol (3 mg kg(-1) i.v.).3 Cooling both vagal nerves produced significant increases in blood pressure, heart rate and spontaneous sympathetic efferent discharge but did not affect the relationship between sympathetic efferent discharge and mean blood pressure or the responses to carotid occlusion. Atenolol significantly reduced blood pressure, heart rate and sympathetic efferent discharge but the change in sympathetic efferent discharge on vagal cooling was less than before giving the drug. Atenolol also attenuated the reflex responses of the sympathetic nerves to changes in blood pressure and reduced responses to carotid occlusion. This attenuation was not removed by vagal cooling.4 Thus, neither the reduction in spontaneous sympathetic efferent discharge nor the attenuation of the baroreceptor reflex seen after atenolol, are due to an increased input to the brain from vagal afferent fibres. Other possible mechanisms whereby atenolol might exert its effects on the sympathetic nerves are discussed.

Non-Markov negative correlation between interspike intervals in mammalian sympathetic efferent discharges

The background discharge of sympathetic efferent fibres in the hypogastric and splanchnic nerves of the cat was analyzed. Stationary discharges were renewal or had significant negative first order serial correlation coefficients. Negatively correlated discharges were non-Markov and the post-spike depression persisted for up to 5 s, covering the same time course as the prolonged inhibitory phenomena of sympathetic reflexes.

The influence of visceral mechanoreceptors on sympathetic efferent discharge in the cat.

1. Recordings have been made from eighty-three single sympathetic efferent units in the hypogastric nerve in two types of preparation. In all animals the baroreceptors were denervated to exclude changes in sympathetic discharge resulting from any variations in arterial pressure, and the spinal cord was sectioned at the 6th lumbar segment to exclude changes in efferent discharge that might have been due to pelvic nerve afferents from the bladder or other viscera. In some animals the afferent pathways were sectioned from all pelvic and lower abdominal viscera other than the bladder, so that the vesical afferent pathway was the only neural pathway that might mediate reflex events from these viscera. The hypogastric nerve afferent pathway was excited by bladder distension or by bladder contractions induced by electrical stimulation of the sacral cord.2. Approximately half the units gave an increase in spike rate during distension or during contraction of the bladder. Three-quarters of the units tested also gave an increase in spike rate during colonic distension. In no units that exhibited convergence of afferent input did colonic and vesical stimuli cause responses of opposite sign.3. Approximately 10% of units showed a reduction in discharge rate when the bladder was distended or caused to contract.4. The estimated intravesical pressure thresholds for these reflexes were in the range 8-56 mmHg which extends beyond that of the mechanoreceptors which form the afferent limb of the reflex.5. These reflex studies indicate that the hypogastric nerve afferents from the bladder can elicit sympathetic reflexes within the physiological range of intravesical pressures, and that vesico-sympathetic reflexes can be elicited in the absence of pelvic nerve afferent inputs.In 75% of sympathetic efferent units that respond to bladder distension or contraction, there is evidence for convergent inputs with similar actions from the colon.