Contrasting reflex influences of cardiac afferent nerves during coronary occlusion

Afferent neurons contained within cardiac sympathetic nerves may have important influences on the circulation when activated during myocardial ischemia. Although such activation is known to reflexly excite upper thoracic sympathetic efferent neurons, effects on other components of sympathetic outflow are unknown. Therefore, cardiac sympathetic afferent nerves were stimulated by occlusion of coronary arteries to investigate their reflex influences on renal sympathetic nerve activity and systemic arterial blood pressure. Responses were observed in anesthetized cats in which sympathetic and/or vagal cardiac afferent nerves remained intact and arterial baroreceptors remained intact or had been denervated. Stimulating sympathetic afferent neurons caused excitation of renal nerve activity, which was accompanied by variable changes in arterial pressure. Stimulation of vagal afferents by coronary occlusion consistently produced inhibition of renal nerve activity and marked depressor responses. When both components of cardiac innervation remained intact, increases or decreases in renal nerve activity and blood pressure were elicited by coronary artery occlusion in the presence or absence of arterial baroreceptors. These results illustrate that cardiac sympathetic afferent nerves can contribute significantly to cardiovascular control during myocardial ischemia.     

Differential pattern of sympathetic outflow during upper airway stimulation with smoke

This study investigates directly the possibility that sympathetic discharge to the heart is decreased while it is increased to other organs during upper respiratory perfusion with cigarette smoke. Blood pressure (BP), heart rate, ECG, and respiratory movements were monitored in urethane-anesthetized rabbits. Insertion of two cannulas allowed respiration of room air while passing smoke across the upper respiratory irritant receptors and out through the nares. Through a retroplural incision, the left stellate ganglion was exposed and a cardiac branch isolated. Similarly, a left renal nerve was isolated. Multiunit nerve recordings were obtained from both nerves. In four control animals, cigarette smoke (50 ml) caused apnea, bradycardia (-116 beats/min) and increased BP (33 mmHg). Activity in the renal nerve increased (248% of control [C]) and activity in the cardiac nerve was reduced (62% C). In these animals after Flaxedil and artificial respiration, nerve activity responses were still pronounced (renal, 178% C; cardiac, 66% C). In four other barodenervated animals neural responses to smoke were similar to those observed with baroreceptors intact (renal, 211% C; cardiac, 51% C). In these animals after artificial ventilation and Flaxedil, responses were not significantly changed. These results indicate that smoke stimulation causes a differential pattern of sympathetic discharge. The responses observed cannot be accounted for by secondary adjustments through arterial baroreceptors, chemoreceptors, or pulmonary stretch receptors.     

Reflex changes in post- and preganglionic sympathetic adrenal nerve activity and postganglionic sympathetic renal nerve activity upon arterial baroreceptor activation and during severe haemorrhage in the rat

Carlsson , S., Skarphedinsson , J. O., Delle , M., Hoffman , P. & Thorén , P. 1992. Reflex changes in post- and preganglionic sympathetic nerve activity and postganglionic sympathetic renal nerve activity upon arterial baroreceptor activation and during severe haemorrhage in the rat. Acta Physiol Scand 144 , 317–323. Received 19 August 1 991 , accepted 18 November 1991. ISSN 0001–6772. Department of Physiology, University of Göteborg, Sweden and Department of Physiology, University of Iceland, Reykjavik, Iceland. The aim of the study was to compare pre- (pre-aSNA) and postganglionic adrenal sympathetic nerve activity (post-aSNA) and postganglionic renal sympathetic nerve activity (rSNA) in rats during arterial baroreceptor activation and haemorrhage. Adrenal multifibre nerve activity was recorded in chloralose-anaesthetized Wistar rats. To test for pre-aSNA or post-aSNA in adrenal nerves, a ganglionic blocker, trimethaphan (10 mg kg^-1), was administered i.v. If the nerve activity in the adrenal nerve decreased or increased the nerve was considered to contain predominantly post-or preganglionic fibres, respectively. In contrast, the renal nerves exhibit an almost pure postganglionic activity. Baroreceptor activity was tested by activation of baroreceptors, with an a-receptor agonist, phenylephrine, which was slowly infused (0.5–2 mUg kg^-1 min-^l), and to deactivate the baroreceptors the rats were bled down to 50 mmHg for 8 min. The experiments showed that all tested nerve types were baroreceptor dependent. There were no significant differences between the slopes relating nerve activity inhibition to increase in blood pressure (infusion of phenylephrine). During maximal inhibition there was a difference between the rSNA and pre-aSNA, 87 ± 4%, n= 6 , and 68±6%, n = 10 (P < 0.01) of the control value, respectively. The maximal inhibition of post-aSNA was 80 ± 3%, n= 7 , of the control value. During haemorrhage there was a difference between the nerve populations. Pre-aSNA responded with a marked increase within 1.5 rnin (159 ± 29% of control, n= 7) and was then maintained at that level until retransfusion. Post-aSNA responded with i transient increase, reaching 158 ± 19% of control after 1.5min but then decreased slowly during the next 3 min, reaching a value of 89 8 76 at 7.5 rnin of haemorrhage. Finally, rSNA (n = 7) responded with an initial increase (peak value 1.5 min 138 ± 16%) followed by an inhibition to a minimum of 74±12% of control. Our conclusion is that the postganglionic adrenal nerves respond in a similar way to postganglionic renal nerves during baroreceptor activation and also show the same pattern of response during haemorrhage. This might indicate that postganglionic fibres to the adrenal gland and postganglionic renal fibres to the kidney have the same target structures, i.e. blood vessels. and postganglionic adrenal fibres might therefore be of importance in adrenal blood flow regulation.     

Reflex changes in post- and preganglionic sympathetic adrenal nerve activity and postganglionic sympathetic renal nerve activity upon arterial baroreceptor activation and during severe haemorrhage in the rat.

The aim of the study was to compare pre- (pre-aSNA) and postganglionic adrenal sympathetic nerve activity (post-aSNA) and postganglionic renal sympathetic nerve activity (rSNA) in rats during arterial baroreceptor activation and haemorrhage. Adrenal multifibre nerve activity was recorded in chloralose-anaesthetized Wistar rats. To test for pre-aSNA or post-aSNA in adrenal nerves, a ganglionic blocker, trimethaphan (10 mg kg-1), was administered i.v. If the nerve activity in the adrenal nerve decreased or increased the nerve was considered to contain predominantly post- or preganglionic fibres, respectively. In contrast, the renal nerves exhibit an almost pure postganglionic activity. Baroreceptor activity was tested by activation of baroreceptors, with an alpha-receptor agonist, phenylephrine, which was slowly infused (0.5-2 micrograms kg-1 min-1), and to deactivate the baroreceptors the rats were bled down to 50 mmHg for 8 min. The experiments showed that all tested nerve types were baroreceptor dependent. There were no significant differences between the slopes relating nerve activity inhibition to increase in blood pressure (infusion of phenylephrine). During maximal inhibition there was a difference between the rSNA and pre-aSNA, 87 +/- 4%, n = 6, and 68 +/- 6%, n = 10 (P less than 0.01) of the control value, respectively. The maximal inhibition of post-aSNA was 80 +/- 3%, n = 7, of the control value. During haemorrhage there was a difference between the nerve populations. Pre-aSNA responded with a marked increase within 1.5 min (159 +/- 29% of control, n = 7) and was then maintained at that level until retransfusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Vagal reflex actions of atrial natriuretic peptide survive physiological but not pathological cardiac hypertrophy in rat

Atrial natriuretic peptide (ANP) enhances cardiac vagal baroreflexes in normotensive animals. In spontaneously hypertensive rats (SHRs) this effect of ANP was absent. The reflex actions of ANP were preserved if hypertrophy was completely prevented in SHRs. However even a small amount of cardiac hypertrophy, with no hypertension, in SHRs was accompanied by a loss of the reflex bradycardic actions of ANP. In the present study, we investigated whether pathophysiological cardiac hypertrophy, induced by one-kidney, one-clip renovascular hypertension (1K-1C; n = 6), or physiological cardiac hypertrophy induced by chronic spontaneous, wheel-running exercise training (n = 7), similarly prevented vagal reflex actions of ANP. Cardiac baroreceptor-activated bradycardia was measured during rapid ramp increases ( approximately 5 s) in blood pressure after bolus doses of methoxamine or vehicle in conscious, chronically instrumented rats during infusions of ANP (50 pmol kg(-1) min(-1)). Compared with uninephrectomised control rats (n = 10), rats with 1K-1C had cardiac hypertrophy (approximately 55% increase in left ventricle:body weight (LV:BW) ratio; P < 0.05) and blunted vagal baroreflex gain (-0.93 +/- 0.18 versus-0.50 +/- 0.13 beats min(-1) mmHg(-1); P < 0.05). ANP did not augment baroreflex function in 1K-1C. Compared with their sedentary controls (n = 7), exercise-trained rats with cardiac hypertrophy ( approximately 20% increase LV:BW ratio; P < 0.05) also had blunted ramp baroreflex bradycardia (-1.28 +/- 0.23 versus-0.57 +/- 0.09 beats min(-1) mmHg(-1); P < 0.05). In contrast, ANP more than doubled baroreflex bradycardia in exercise-trained rats (P < 0.05). The aetiology of cardiac hypertrophy therefore influenced whether ANP retained its vagal baroreflex enhancing properties.     

Acute adenosine increases cardiac vagal and reduces sympathetic efferent nerve activities in rats

Adenosine is the first drug of choice in the treatment of supraventricular arrhythmias. While the effects of adenosine on sympathetic nerve activity (SNA) have been investigated, no information is available on the effects on cardiac vagal nerve activity (VNA). We assessed in rats the responses of cardiac VNA, SNA and cardiovascular variables to intravenous bolus administration of adenosine. In 34 urethane-anaesthetized rats, cardiac VNA or cervical preganglionic sympathetic fibres were recorded together with ECG, arterial pressure and ventilation, before and after administration of three doses of adenosine (100, 500 and 1000 μg kg(-1)). The effects of adenosine were also assessed in isolated perfused hearts (n = 5). Adenosine induced marked bradycardia and hypotension, associated with a significant dose-dependent increase in VNA (+204 ± 56%, P < 0.01; +275 ± 120%, P < 0.01; and +372 ± 78%, P < 0.01, for the three doses, respectively; n = 7). Muscarinic blockade by atropine (5 mg kg(-1), i.v.) significantly blunted the adenosine-induced bradycardia (-56.0 ± 4.5%, P < 0.05; -86.2 ± 10.5%, P < 0.01; and -34.3 ± 9.7%, P < 0.01, respectively). Likewise, adenosine-induced bradycardia was markedly less in isolated heart preparations. Previous barodenervation did not modify the effects of adenosine on VNA. On the SNA side, adenosine administration was associated with a dose-dependent biphasic response, including overactivation in the first few seconds followed by a later profound SNA reduction. Earliest sympathetic activation was abolished by barodenervation, while subsequent sympathetic withdrawal was affected neither by baro- nor by chemodenervation. This is the first demonstration that acute adenosine is able to activate cardiac VNA, possibly through a central action. This increase in vagal outflow could make an important contribution to the antiarrhythmic action of this substance.     

Effects of hypovolaemia or isoprenaline infusion on the sympathetic reflex response to PEEP ventilation in rats

The aim of this investigation was to study vagally mediated sympathetic reflex responses to mechanical ventilation with positive end-expiratory pressure (PEEP), during hypovolaemia or during high inotropic stimulation of the heart by isoprenaline infusion. Renal sympathetic nerve activity (RSNA), heart rate and mean arterial pressure were studied during mechanical ventilation with zero end-expiratory pressure (ZEEP) and 5 and 10 cmH₂O PEEP in chloralose anaesthetized Wistar rats. Experiments were performed on two groups of rats: eight animals were subjected to 10% blood volume depletion, and seven animals to infusion of isoprenaline. PEEP ventilation was applied during control conditions and during hypovolaemia or isoprenaline infusion before and after vagotomy. In the intact (control) situation, there was a significant increase in RSNA from ZEEP to 10 PEEP in both groups (+ 75%, + 51%). During hypovolaemia or isoprenaline infusion, PEEP ventilation did not induce any significant increase in RSNA in both groups after vagotomy, 10 PEEP induced a significant increase in both groups (+ 56%, +54%). These results indicated that under conditions of hypovolaemia or increased cardiac inotropism, PEEP ventilation may elicit a vagally mediated reflex with an inhibitory action on sympathetic activity, in turn probably caused by an activation of left ventricular receptors.     

Renal sympathetic activity in spontaneously hypertensive rats and normotensive controls, as studied by three different methods

Recordings of sympathetic activity from multifibre preparations of renal nerves have produced conflicting results concerning the presence or absence of an increased sympathetic discharge in spontaneously hypertensive rat (SHR) compared to normotensive Wistar-Kyoto rats (WKY). Therefore, recordings of single fibre activity to the kidney were performed in anesthetized SHR and WKY in comparison with multifibre recordings in conscious, undisturbed rats. A new method of estimating sympathetic discharge by analyzing the variability of "cycle activity" in multifibre nerve recordings was also used. The average nerve activity in a great number of cardiac cycles was then expressed in relation (in per cent) to the nerve activity in a small number of cardiac cycles with the highest and lowest nerve activity in each rat. Single fibre recordings showed a significantly higher sympathetic activity to the kidneys in SHR (3.8 +/- 0.3 Hz) than in WKY (1.7 +/- 0.2 Hz; p less than 0.001). Also average "cycle activity" was significantly higher in conscious SHR (34 +/- 1%) than in WKY (26 +/- 2%, p less than 0.01). This was due to the larger number of cardiac cycles in SHR with high sympathetic activity while WKY showed more of "silent" cardiac cycles which lacked nerve impulses. Further, the recordings of rectified multifibre renal nerve activity also showed an elevated sympathetic activity in conscious SHR rats. The increased renal sympathetic activity appears to reflect the "primary" central nervous "hyperreactivity" characterizing SHR hypertension. It is suggested that the increased renal sympathetic activity may be of particular importance for the development of primary hypertension in SHR and perhaps also in man.     

Enhanced sympathetic activity and cardiac sympathetic afferent reflex in rats with heart failure induced by adriamycin

Our previous studies have shown that the cardiac sympathetic afferent reflex is enhanced in rats with chronic heart failure(CHF) induced by coronary artery ligation and contributes to the over-excitation of sympathetic activity.We sought to determine whether sympathetic activity and cardiac sympathetic afferent reflex were enhanced in adriamycin-induced CHF and whether angiotensin II(Ang II) in the paraventricular nucleus(PVN) was involved in enhancing sympathetic activity and cardiac sympathetic afferent reflex.Heart failure was induced by intraperitoneal injection of adriamycin for six times during 2 weeks(15 mg/kg).Six weeks after the first injection,the rats underwent anesthesia with urethane and α-chloralose.After vagotomy and baroreceptor denervation,cardiac sympathetic afferent reflex was evaluated by renal sympathetic nerve activity and mean arterial pressure(MAP) response to epicardial application of capsaicin(1.0 nmol).The response of MAP to ganglionic blockade with hexamethonium in conscious rats was performed to evaluate sympathetic activity.The renal sympathetic nerve activity and cardiac sympathetic afferent reflex were enhanced in adriamycin rats and the maximum depressor response of MAP induced by hexamethonium was significantly greater in adriamycin rats than that in control rats.Bilateral PVN microinjection of angiotensin II(Ang II) caused larger responses of the cardiac sympathetic afferent reflex,baseline renal sympathetic nerve activity and MAP in adriamycin rats than control rats.These results indicated that both sympathetic activity and cardiac sympathetic afferent reflex were enhanced and Ang II in the PVN was involved in the enhanced sympathetic activity and cardiac sympathetic afferent reflex in rats with adriamycin-induced heart failure.     

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

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

Effects of sex and ovarian hormones on the initial renal sympathetic nerve activity response to myocardial infarction

The physiological mechanisms contributing to sex differences following myocardial infarction (MI) are poorly understood. Given the strong relationship between sympathetic nerve activity (SNA) and outcome, we hypothesized there may be a sex difference in SNA responses to MI. In anaesthetized, open-chest male, female and ovariectomized (OVX) female Wistar rats, mean arterial pressure, heart rate and renal SNA were recorded in response to ligation of the left coronary artery. In males, renal SNA increased by 30 ± 6% in the first minute of coronary occlusion (P < 0.05) and remained elevated at 18 ± 7% above baseline (P < 0.05) at 2 h following MI. In response to MI, ovary-intact females displayed no change in renal SNA, whereas OVX females displayed a significant increase, similar to that seen in the males (increases of 43 ± 11% at 1 min and 21 ± 7% at 2 h post-MI, P < 0.05 versus intact females). Arterial baroreflex control of renal SNA had a smaller range in females (ovary intact and OVX) than males; no changes in arterial baroreflex responses were observed 1 h post-MI in males or females. Denervating the arterial baroreceptors abolished the renal SNA response to MI in the males, whereas in ovary-intact females and OVX females the response was unaltered. These findings suggest that ovarian hormones are able to blunt the initial sympathetic activation post-MI in females and that the importance of the arterial baroreflex in mediating initial sympathetic activation post-MI is different between the sexes.     

Characteristics of renal sympathetic nerve activity in experimental congestive heart failure in the rat

Recently emerging evidence has indicated that efferent renal sympathetic nerve activity (RSNA) is increased in congestive heart failure (CHF). In the present study the cyclic activity of the renal nerve in the normal and CHF rat was studied. An ischaemic myocardial lesion resulting in CHF was induced by left coronary artery ligation. Sham-operated rats subjected to thoracotomy served as normal controls. Renal sympathetic nerve activity was recorded under chloralose anaesthesia. The neural cycle activity was significantly higher in CHF (47 ±3%) compared with sham-operated rats (34 + 3%, P < 0.005). Baroreceptor control of RSNA was significantly attenuated in CHF compared with normal control rats (P < 0.005). In response to noxious thermal stimulation by 48^oC water immersion of the tail tip, the increase of RSNA was significantly higher in CHF compared with sham-operated rats. A stepwise 15% blood volume expansion over 5 min which induced no alterations of blood pressure or heart rate (HR) resulted in a gradual decrease of RSNA in control rats by approximately 25% at the end of the volume expansion procedure. In CHF rats however, there was no significant change in RSNA during volume expansion. It is concluded that in CHF rats: (1) efferent RSNA is increased; (2) baroreceptor control of RSNA is decreased; (3) RSNA in response to cutaneous thermal noxious stimulation is exaggerated; and (4) RSNA inhibition by cardiopulmonary receptors is blunted.     

Renal sympathetic nerve activity during morphine abstinence in sino-aortic baroreceptor-denervated rats

This study was undertaken to investigate the influence of the arterial baroreceptors on the response of renal sympathetic nerve activity (rSNA) during naloxone-precipitated morphine abstinence in rats. In chronically baroreceptor-denervated, morphine-dependent rats, rSNA, mean arterial pressure (MAP) and heart rate (HR) were studied before and after repeated i.v. bolus doses of naloxone (0.005–5 mg kg^-1), during chloralose anaesthesia or in the conscious state. In the anaesthetized animals, naloxone doses of 0.05–5 mg kg^-1 caused a pronounced inhibition of rSNA, reaching a level 61 % below pre-naloxone activity. This was accompanied by increases in MAP and HR. In the conscious rats, the lower doses of naloxone elicired an initial state of increased somatomotor activity. This was paralleled by slight increases in rSNA and MAP. After 4–5 min, the behavioural excitation faded and was replaced by lethargy. The rats exhibited still signs of withdrawal in the form of piloerection, chromodacryorrhoea and defaecations. Concomitantly, rSNA returned towards the pre-naloxone level, while MAP showed a sustained increase. The higher naloxone doses exacerbated the hypertension without any further changes in rSNA or in behaviour. We conclutle that the influence of the baroreceptors is of minor significance for the inhibition of rSNA during naloxone-precipitated abstinence in anaesthetized rats. In conscious, intact rats, however, the baroreceptors seem to contribute to rSNA inhibition since no significance decrease of rSNA occurred in baroreceptor-denervated rats in the present study. This is in contrast to our previous finding of a marked inhibition of rSNA in rats with intact baroreceptors.     

The effect of baroreceptors on the latency of evoked responses in sympathetic nerves during the cardiac cycle

1. A rapid increase in pressure in a vascularly isolated perfused carotid sinus has been shown to inhibit a reflex response in efferent sympathetic nerves of the dog evoked by electrical stimulation of the radial nerve.2. In intact preparations with the carotid baroreceptors innervated, the mean latency and the variance of the latency of reflex sympathetic nerve responses was reduced when the stimuli evoking the responses were applied at one point of both cardiac and respiratory cycles. When the baroreceptors were denervated there were no significant differences in the responses to random and synchronized stimuli.3. In intact preparations the latency of evoked responses in sympathetic nerves was found to vary progressively during a cardiac cycle; the maximum increase in latency was observed with the responses that occurred at that phase of the cardiac cycle when the baroreceptors exert maximal inhibition on spontaneous sympathetic activity. After denervation of the carotid sinuses a much smaller change during the cardiac cycle was still present, possibly due to effects produced by baroreceptors of the aortic arch and elsewhere.4. It was concluded that changes in baroreceptor activity, due to beat to beat fluctuations of the systemic arterial pressure are a major factor causing variations in the latency of responses in sympathetic nerves evoked by stimuli applied to a cutaneous nerve.     

Responses of neurons in paraventricular nucleus to activation of cardiac afferents and acute myocardial ischaemia in rats

Stimulation of cardiac sympathetic afferents increases sympathetic outflow and blood pressure. Chemicals released during myocardial ischaemia activate cardiac afferents. This study was to determine the responses of neurons in paraventricular nucleus (PVN) to the cardiac afferent activation caused by exogenous chemicals or myocardial ischaemia using an extracellular single-unit recording method. Rats were anaesthetized and underwent bilateral cervical vagal denervation (VD) and carotid and aortic baroreceptor denervation (BD). In 196 spontaneously active neurons in parvicellular PVN, 60 (30.6%), 36 (18.4%) and 91 (46.4%) neurons were respectively sensitive, mildly sensitive and insensitive to capsaicin, while nine (4.6%) neurons showed inhibitory responses to capsaicin. Epicardial application of capsaicin activated capsaicin-sensitive neurons in the PVN and increased mean arterial pressure. These neurons were also sensitive to exogenous bradykinin, adenosine and H(2)O(2). The neuron response is not secondary to a capsaicin-induced increase in mean arterial pressure because a similar degree of pressor response induced by aortic coarctation did not increase the neuron activity. Compared with intact rats, VD or BD or combined VD and BD increased the response of capsaicin-sensitive neurons to epicardial application of capsaicin, while stimulation of vagal afferents inhibited the response. Myocardial ischaemia caused increases in the activity of capsaicin-sensitive neurons and renal sympathetic nerve activity. The results indicate that chemical stimulation of cardiac sympathetic afferents activates capsaicin-sensitive neurons in parvicellular PVN, which is inhibited by the afferent activities of vagi and arterial baroreceptors. Acute myocardial ischaemia activates capsaicin-sensitive neurons in PVN and enhances sympathetic outflow.     

Prevention of exercise-induced cardiac hypertrophy in rats by chemical sympathectomy (guanethidine treatment)

The effect of 'chemical sympathectomy', produced by daily intraperitoneal injections of guanethidine sulphate for six weeks, was studied in sedentary rats and in rats chronically exercised by swimming. The guanethidine-treatment itself caused the following changes. There was a reduction in the rate of weight gain resulting in a 7% lower final body weight. Organ content of noradrenaline was decreased by 90% in spleen and submandibular glands and by 83% in the heart. Urinary excretion of noradrenaline was also decreased, but to a lesser degree, both during rest (45% lower) and after acute exercise (46% lower), while the urinary excretion of adrenaline was no different from that of controls. There was a compensatory adrenal hypertrophy in the guanethidine-treated rats, with a significant increase in adrenal catecholamine levels that was more pronounced for noradrenaline (+45%) than for adrenaline (+11%). Chronic physical exercise produced the expected degree of cardiac hypertrophy in untreated rats, but this adaptive cardiac hypertrophy was completely absent in the exercised guanethidine-treated rats. The results indicate, firstly that a good degree of chemical sympathectomy was obtained and that the persistence of a considerable urinary excretion of catecholamines in the guanethidine-treated rats was due to a compensatory increase in the secretory activity of the adrenal medulla. Secondly, it is suggested that the adaptive cardiac hypertrophy produced by chronic exercise is not caused by a direct effect of the increased work load on the cardiac muscle cell, but is instead mediated by release of a trophic factor from cardiac sympathetic nerves, probably noradrenaline itself but possibly a secretory protein.     

Influence of arterial baroreceptors and intracerebroventricular guanabenz on synchronized renal nerve activity

The contributions of changes in the number of active fibres and the peak interval of synchronized neural discharges to arterial baroreflex regulated alterations in renal sympathetic nerve activity were examined in intact conscious rats. Stimulation of central nervous system α₂ adrenoreceptors with intracerebroventricular guanabenz (10, 20, 40 μg) was used to alter renal sympathetic nerve activity by a non-reflex mechanism in both intact and sinoaortic denervated (SAD) rats. Synchronized renal sympathetic nerve discharge was analysed with the sympathetic peak detection algorithm. When arterial pressure was increased from 50 mmHg to 150 mmHg in intact rats, the peak height (number of simultaneously active fibres) of synchronized discharges decreased in a sigmoidal fashion while the peak interval remained unchanged. Guanabenz produced a dose dependent inhibition of renal sympathetic nerve activity due to both a decrease in peak height and an increase in peak interval of synchronized discharges in both intact and SAD rats. Arterial baroreflex mediated changes in renal sympathetic nerve activity are due to changes in the number of simultaneously active nerve fibres. Central nervous system α₂ adrenoreceptor stimulation decreases renal sympathetic nerve activity by decreasing the number of active fibres and increasing the peak interval, acting on additional neural pathways not involved in buffering acute arterial pressure changes.     

Baroreceptor and somatic sensory regulation of kidney function in two-kidney, one-clip Goldblatt hypertensive rats.

The aim of this investigation was to characterize the renal haemodynamic and tubular responses to somatic afferent nerve stimulation following the removal of afferent nerve input from the atria or the carotid sinuses in chloralose-urethane-anaesthetized Sprague-Dawley rats and two-kidney, one-clip Goldblatt hypertensive rats. Bilateral stimulation of the brachial nerve plexi at 15 V, 1.3 Hz for 0.2 ms resulted in an increase in systemic blood pressure in each group of 10-40%, while renal perfusion pressure was maintained at a constant level. There were significantly larger falls in left renal blood flow and combined left and right glomerular filtration rate in all groups following selective denervation of either the cardiopulmonary or the carotid sinus baroreceptors, respectively. Brachial nerve stimulation decreased urine flow rate and absolute and fractional sodium excretion from both kidneys in Sprague-Dawley intact animals by 53, 65 and 59%; in vagotomized animals by 68, 77 and 63%; and in carotid sinus denervated animals by 86, 90 and 48%, respectively. The renal response in the Goldblatt group were similar to the normotensive group, but the main contribution of the total response was from the untouched left kidney. The inhibitory influence of the vagus and carotid sinuses on the renal sympathetic nerve-mediated sodium and water resorption appeared to be enhanced in the Goldblatt hypertensive rats when compared with the normotensive rats. The renal functional responses to somatic afferent nerve stimulation appeared to be well preserved in the renovascular hypertensive rats, although there were important differences in the contributions to the responses from the left and right kidneys. Furthermore, the baroreceptors exerted a greater influence on basal renal function in the hypertensive rats.     

Central command: control of cardiac sympathetic and vagal efferent nerve activity and the arterial baroreflex during spontaneous motor behaviour in animals

Feedforward control by higher brain centres (termed central command) plays a role in the autonomic regulation of the cardiovascular system during exercise. Over the past 20 years, workers in our laboratory have used the precollicular-premammillary decerebrate animal model to identify the neural circuitry involved in the CNS control of cardiac autonomic outflow and arterial baroreflex function. Contrary to the traditional idea that vagal withdrawal at the onset of exercise causes the increase in heart rate, central command did not decrease cardiac vagal efferent nerve activity but did allow cardiac sympathetic efferent nerve activity to produce cardiac acceleration. In addition, central command-evoked inhibition of the aortic baroreceptor-heart rate reflex blunted the baroreflex-mediated bradycardia elicited by aortic nerve stimulation, further increasing the heart rate at the onset of exercise. Spontaneous motor activity and associated cardiovascular responses disappeared in animals decerebrated at the midcollicular level. These findings indicate that the brain region including the caudal diencephalon and extending to the rostral mesencephalon may play a role in generating central command. Bicuculline microinjected into the midbrain ventral tegmental area of decerebrate rats produced a long-lasting repetitive activation of renal sympathetic nerve activity that was synchronized with the motor nerve discharge. When lidocaine was microinjected into the ventral tegmental area, the spontaneous motor activity and associated cardiovascular responses ceased. From these findings, we conclude that cerebral cortical outputs trigger activation of neural circuits within the caudal brain, including the ventral tegmental area, which causes central command to augment cardiac sympathetic outflow at the onset of exercise in decerebrate animal models.     

Renal sympathetic nerve activity is increased in monosodium glutamate induced hyperadipose rats

The literature suggests that both obesity and hypertension are associated with increased sympathetic nerve activity. In the present study we evaluated the renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate (HR) in hyperadipose rats induced by neonatal administration of monosodium glutamate (MSG). Neonatal Wistar male rats were injected with MSG (4 mg/g body weight ID) or equimolar saline (control) for 5 days. At 90th day, all rats were anesthetized (urethane 1.4 g/kg) and prepared for MAP, HR and renal sympathetic nerve activity recordings. The anesthetized MSG rats presented baseline hypertension and increased baseline RSNA compared with control. Our results suggest the involvement of the renal sympathetic nervous system in the physiopathology of the MSG obesity.