Centrally evoked sympathetic discharge: a functional study of medullary vasomotor areas

1. The medulla oblongata was stimulated electrically in decerebrate cats following bilateral vagotomy. Changes in splanchnic nerve discharge evoked by stimulation of pressor and depressor areas in the medulla are correlated with changes in arterial pressure. An interaction of baroreceptor afferents with the efferent sympathetic system at the level of the medulla and/or spinal cord is demonstrated. Evidence is presented which suggests that it is possible to alter activity selectively in a given division (splanchnic) of the sympathetic outflow.

2. Evoked responses were categorized as follows:

(a) Sustained splanchnic activation; an immediate increase in total splanchnic activity occurred with only a small, gradual decline in activity during the stimulation period. Mild stimulation (150-200 μA) raised systolic pressure by 60-80 mm Hg and stronger stimulation (300-400 μA) increased pressure by 100-150 mm Hg. When comparable pressor responses were elicited from points on either side of the mid line, splanchnic excitation was greater with homolateral stimulation (left side).

(b) Unsustained splanchnic activation; an immediate increase in activity occurred which declined sharply as systolic pressure rose by 60-100 mm Hg during stimulation. Such a decline was attributed to the influence of baroreceptor afferents. Thus, if previous carotid occlusion was maintained during stimulation, the decline in activity was minimized although the pressor response increased. It is suggested that the structures yielding unsustained responses differ from those yielding sustained responses in their functional relation with the baroreceptor afferents.

(c) Reduced splanchnic discharge during direct medullary stimulation; a partial or complete inhibition of splanchnic activity was obtained, which was sometimes accompanied by a 20-40 mm Hg reduction in systolic pressure. However, the direction and magnitude of the systemic pressure change were not as consistently related to the splanchnic response as they were during activation. Even if splanchnic efferent activity were elevated by carotid occlusion, stimulation still reduced discharge.

     

Responses of adrenal sympathetic nerve activity and catecholamine secretion to cutaneous stimulation in anesthetized rats

Reflex effects of cutaneous mechanical stimulation on adrenal sympathetic efferent nerve activity and secretion rates of the adrenal medullary hormones (epinephrine and norepinephrine) were studied in anesthetized rats. Noxious pinching stimulation of the lower chest or hindpaw skin for 3 min produced proportional reflex increases in both the nerve activity and secretion rates of epinephrine and norepinephrine from the adrenal medulla in animals with an intact central nervous system. However, lower chest stimulation elicited a longer lasting response than hindpaw stimulation, 7-17 min vs 1 min after cessation of the stimulation, respectively. After spinal transection at the C1-2 level, only lower chest stimulation was capable of producing a reflex response, lasting 1 min after cessation of the stimulation. Contrary to the responses elicited by pinching, non-noxious brushing stimulation of the lower chest or hindlimb skin for 3 min in animals with an intact central nervous system produced proportional reflex decreases in nerve activity and epinephrine and norepinephrine secretion rates during the stimulation period only. Some slight increases in both nerve activity and secretion rates, lasting several minutes, followed cessation of the stimulation. However, in spinalized animals, non-noxious lower chest or hindlimb stimulation produced opposite effects, increasing both the nerve activity and secretion rates of epinephrine and norepinephrine. In spinalized animals lower chest brushing stimulation elicited a much stronger response than hindlimb brushing stimulation. It was concluded that; (1) the secretion of adrenal medullary hormones can be controlled reflexly by mechanical cutaneous stimulation through the central nervous system via adrenal sympathetic efferent nerves; (2) the excitatory effect of the cutaneo-adrenal medullary reflexes was independent of noxious or non-noxious stimulation at the spinal level, whereas in rats with an intact central nervous system the effect was either excitatory or inhibitory in response to noxious or non-noxious stimulation, respectively; (3) there is a marked segmental organization of this reflex at the spinal level which is modified into a generalized response through supraspinal central structures.     

Changes in renal sympathetic outflow during hypotensive haemorrhage in rats

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

Superior laryngeal nerve section abolishes capsaicin evoked chemoreflex in anaesthetized rats

Respiratory effects of an intravenous injection of capsaicin were investigated in nine vagotomized and subsequently laryngeally deafferentated, urethane- and chloralose-anaesthetized and spontaneously breathing rats. Bolus injection of capsaicin (5 micrograms/kg) into the right femoral vein induced an expiratory apnoea of 4.23 +/- 0.63 s duration (mean +/- SEM). In post-apnoeic breathing, tidal volume increased by 14% from the control level (P < 0.05) in all nine rats treated by vagotomy. Section of the superior laryngeal nerves (SLNs) precluded the occurrence of apnoea. Results of this study indicate that in vagotomized rats sensory input from the larynx constitutes an important pathway to the nodose ganglia endowed with capsaicin receptors.     

Pepsin secretion in the anaesthetized cat and the effect of sympathetic nerve stimulation.

1. Experiments were performed on chloralose anaesthetized cats and gastric mucosal blood flow, acid and pepsin secretions were measured. Gastric mucosal pepsin and protein contents were measured at the end of the experiments which were done in three groups: gastrin (A), vagal (B), vagal and sympathetic nerve (C) stimulations. 2. Vagal stimulation significantly reduced (76%) the pepsin content of gastric mucosa compared with gastrin stimulated animals, none of which secreted pepsin. 3. The sum of the secreted and extracted pepsins for all the three groups was not significantly different. There was no significant difference in the extracted protein from any of the groups. 4. Gastric mucosal blood flow, acid and pepsin outputs all had significant correlations with time during the first 70 min of vagal stimulation. During the period 80-160 min of vagal stimulation acid secretion and mucosal blood flow were not correlated with time but pepsin output declined significantly. From 170 to 220 min of vagal stimulation, acid and pepsin outputs and mucosal blood flow were not correlated with time. 5. The assumed pepsin store during each period was calculated and after 40 min of vagal stimulation there is a constant percentage pepsin output from this assumed store. 6. There is some data to suggest that pepsinogen synthesis was occurring during the period 170-220 min of vagal stimulation. 7. Sympathetic nerve stimulation which started at 160 min after the beginning of sustained vagal stimulation, significantly inhibited gastric acid secretion and mucosal blood flow, and in addition it significantly inhibited pepsin secretion. This is consistent with the hypothesis that sympathetic nerve inhibition of gastric mucosal function is mediated by a vasoconstrictor mechanism.     

Reduced sympathetic outflow and adrenal secretory activity during a 40-day stay in the Antarctic.

Human adaptation to unknown and extreme environments requires changes in the psychological and physical homeostasis. We previously reported a significant decrease of anterior pituitary and adrenal hormonal levels and a significant modification of psychophysiological correlates of stress, such as galvanic skin response, after exposure to Antarctica, suggesting a possible decrease of individual arousal. The latter was hypothesized to be correlated with a modification of autonomic balance, mainly represented by a possible reduction of adrenergic output. The aim of the present study was to assess the patterns of hormonal circadian rhythms and the autonomic nervous system balance by means of spectral analysis of heart rate variability (HRV). These parameters were evaluated during 3 sessions (baseline, session 1 and session 2), before, at the beginning and after a 40-day stay in Antarctica (Station of Terra Nova Bay; average temperature in the study period: -11 degrees C, 24 h of light, sea level). In each of the sessions, 6 healthy male subjects underwent a 24-h electrocardiogram and blood sampling (08.00, 12.00, 16.00, 20.00, 24.00 and 08.00 h) for hormonal determinations. The data showed a remarkable decrease of hormonal levels without significant changes in circadian rhythms. Spectral analysis of HRV showed an imbalance of the autonomic nervous system with a relative significant decrease of the low frequency band (0.1 Hz) in session 1 and 2 compared to baseline, which can be functionally interpreted as a relative decrement of the sympathetic component. In conclusion, the exposure to a cold and extreme environment seems to affect autonomic balance over a 40-day period. This is followed by a significant reduction of the anterior pituitary and adrenal hormonal secretory patterns with preserved hormonal circadian rhythms (within the same time period of 40 days). This pattern is suggestive of a trophotropic neurovegetative adaptive process.     

Effect of hypothermia on baroreflex control of heart rate and renal sympathetic nerve activity in anaesthetized rats

The present study investigated the effect of acute hypothermia on baroreflex control of heart rate (HR) and renal sympathetic nerve activity (RSNA) by generating baroreflex logistic function curves, using bolus doses of phenylephrine and sodium nitroprusside, in anaesthetized male Wistar rats at a core temperature ( T _b) of 37°C, during acute severe hypothermia at T _b= 25°C and on rewarming to 37°C. Comparisons were made between rats without (euthermic, n = 6) and with (acclimated, n = 7) prior exposure to lower ambient temperatures and shorter photoperiod, simulating adaptation to winter conditions. In both groups of rats, acute hypothermia to T _b= 25°C shifted the baroreflex-RSNA curve slightly leftwards and downwards with decreases in the setpoint pressure and maximal gain, whereas it markedly impaired the baroreflex-HR curve characterized by decreases in response range by ∼90% ( P < 0.001), minimum response by ∼10% ( P < 0.05) and maximum gain by ∼95% ( P < 0.001), from that at T _b= 37°C. All parameters were restored to precooling levels on rewarming. Electrical stimulation of cardiac vagal efferents induced a voltage-related bradycardia, the magnitude of which was partially reduced during acute hypothermia, and there was a significant prolongation of the electrocardiogram intervals indicating a delay in cardiac conduction. Mild suppression of baroreflex control of RSNA could contribute to hypothermic hypotension and may primarily reflect an effect of T _b on central drive. The marked attenuation of the baroreflex control of HR during hypothermia was likely to be due to an impairment of both the central and peripheral components of the reflex arc. Baroreflex control of RSNA and HR was similar between both groups of rats, which implied that the control was non-adaptive on chronic cold exposure.     

Reflex responses evoked in the adrenal sympathetic nerve to electrical stimulation of somatic afferent nerves in the rat

The present study was initiated to determine the role of somatic A (myelinated) and C (unmyelinated) afferent fibers in both responses of increases and decreases in adrenal sympathetic nerve activities during repetitive mechanical pinching and brushing stimulations of the skin in anesthetized rats with central nervous system (CNS) intact. Accordingly, changes in adrenal sympathetic nerve activity resulting from repetitive and single shock electrical stimulation of various spinal afferent nerves, especially the 13th thoracic (Th13) spinal nerve and the sural nerve, were examined in urethane/chloralose-anesthetized rats. Repetitive electrical stimulation of A afferent fibers in Th13 spinal or sural nerve decreased the adrenal nerve activity similarly as brushing stimulation of skin of the lower chest or hindlimb did, while repetitive stimulation of A plus C afferent fibers of those nerves increased the adrenal nerve activity as pinching stimulation of those skins did. Single shock stimulation of spinal afferent nerves evoked various reflex components in the adrenal nerve: an initial depression of spontaneous activity (the early depression); the following reflex discharge due to activation of A afferent fibers (the A-reflex); a subsequent reflex discharge due to activation of C afferent fibers (the C-reflex); and following post-excitatory depressions. These reflexes seem to be mediated mainly via supraspinal pathways since they were abolished by spinal transection at the C1-2 level. Although the supraspinal A- and C-reflexes could be elicited from stimulation of a wide variety of spinal segmental afferent levels, the early depression was more prominent when afferents at spinal segments closer to the level of adrenal nerve outflow were excited. It is suggested that the decreased responses of the adrenal nerve during repetitive electrical stimulation of A afferent nerve fibers are attributable to summation of both the early depression and post-excitatory depression evoked by single shock stimulation, while the increased responses during repetitive stimulation of A plus C afferent fibers are attributable to summation of the C-reflex after single shock stimulation. In spinalized rats, repetitive stimulation of Th13 always increased the adrenal nerve activities regardless of whether A fibers alone or A plus C fibers were stimulated, just as brushing and pinching of the lower chest skin always increased them. The increased responses in spinal animals seem to be related to the fact that single electrical stimuli of Th13 produced A- and C-reflexes of spinal origin without clear depressions.     

Impact of cardiac hypertrophy on arterial and cardiopulmonary baroreflex control of renal sympathetic nerve activity in anaesthetized rats

This study aimed to quantify the effect of cardiac hypertrophy induced with isoprenaline and caffeine on reflex regulation of renal sympathetic nerve activity by the arterial and cardiopulmonary baroreceptors. Male Wistar rats, untreated or given water containing caffeine and subcutaneous (s.c.) isoprenaline every 72 h for 2 weeks or thyroxine s.c. for 7 days, were anaesthetized and prepared for measurement of renal sympathetic nerve activity or cardiac indices. Both isoprenaline-caffeine and thyroxine treatment blunted weight gain but increased heart weight and heart weight to body weight ratio by 40 and 14% (both P < 0.01), respectively. In the isoprenaline-caffeine group, the maximal rate of change of left ventricular pressure and the contractility index were higher by 17 and 14% (both P < 0.01), respectively, compared with untreated rats. In the isoprenaline-caffeine-treated rats, baroreflex gain curve sensitivity was depressed by approximately 30% (P < 0/05), while the mid-point blood pressure was lower, by 15% (P < 0/05), and the range of the curve was 60% (P < 0.05) greater than in the untreated rats. An acute intravenous infusion of a saline load decreased renal sympathetic nerve activity by 42% (P < 0.05) in the untreated rats but had no effect in the isoprenaline-caffeine- or the thyroxine-treated groups. The isoprenaline-caffeine treatment induced cardiac hypertrophy with raised cardiac performance and an associated depression in the reflex regulation of renal sympathetic nerve activity by both high- and low-pressure baroreceptors. The thyroxine-induced cardiac hypertrophy also blunted the low-pressure baroreceptor-mediated renal sympatho-inhibition. These findings demonstrate that in cardiac hypertrophy without impaired cardiac function, there is a blunted baroreceptor control of renal sympathetic outflow.     

Nitric oxide-dependent protein synthesis in parotid and submandibular glands of anaesthetized rats upon sympathetic stimulation or isoprenaline administration

In anaesthetized female rats, the beta-adrenoceptor agonist isoprenaline was intravenously infused (20 microg kg(-1) min(-1)) for 30 min or the ascending cervical sympathetic nerve trunk was intermittently stimulated (50 Hz, 1 s every tenth second) on one side for 30 min. The incorporation of [3H]leucine into trichloroacetic acid (TCA)-insoluble material was used as an index of protein synthesis. In response to isoprenaline, the [3H]leucine incorporation increased by 79% in the parotid glands and by 82% in the submandibular glands. The neuronal type NO-synthase inhibitor N-PLA, reduced (P < 0.001) this response to 26% and 20%, respectively. Sympathetic stimulation under alpha-adrenoceptor blockade increased the [3H]leucine incorporation by 192% in the parotid glands and by 35% in the submandibular glands. N-PLA reduced the corresponding percentage figures to 86% (P < 0.01) and 8% (P < 0.05). When tested in the parotid glands, the non-selective NO-synthase inhibitor L-NAME reduced (P < 0.01) the nerve-evoked response to 91%. The increase in [3H]leucine incorporation in response to sympathetic stimulation under beta-adrenoceptor blockade was not affected by N-PLA in the parotid (139% versus 144%) and submandibular glands (39% versus 34%). In non-stimulated glands, the [3H]leucine incorporation was not influenced by the NO-synthase inhibitors. In conclusion, beta-adrenoceptor mediated salivary gland protein synthesis is largely dependent on NO generation by neuronal type NO-synthase, most likely of parenchymal origin.     

Increased sympathetic outflow in juvenile rats submitted to chronic intermittent hypoxia correlates with enhanced expiratory activity

Chronic intermittent hypoxia (CIH) in rats produces changes in the central regulation of cardiovascular and respiratory systems by unknown mechanisms. We hypothesized that CIH (6% O₂ for 40 s, every 9 min, 8 h day⁻¹) for 10 days alters the central respiratory modulation of sympathetic activity. After CIH, awake rats ( n = 14) exhibited higher levels of mean arterial pressure than controls (101 ± 3 versus 89 ± 3 mmHg, n = 15, P < 0.01). Recordings of phrenic, thoracic sympathetic, cervical vagus and abdominal nerves were performed in the in situ working heart–brainstem preparations of control and CIH juvenile rats. The data obtained in CIH rats revealed that: (i) abdominal (Abd) nerves exhibited an additional burst discharge in late expiration; (ii) thoracic sympathetic nerve activity (tSNA) was greater during late expiration than in controls (52 ± 5 versus 40 ± 3%; n = 11, P < 0.05; values expressed according to the maximal activity observed during inspiration and the noise level recorded at the end of each experiment), which was not dependent on peripheral chemoreceptors; (iii) the additional late expiratory activity in the Abd nerve correlated with the increased tSNA; (iv) the enhanced late expiratory activity in the Abd nerve unique to CIH rats was accompanied by reduced post-inspiratory activity in cervical vagus nerve compared to controls. The data indicate that CIH rats present an altered pattern of central sympathetic–respiratory coupling, with increased tSNA that correlates with enhanced late expiratory discharge in the Abd nerve. Thus, CIH alters the coupling between the central respiratory generator and sympathetic networks that may contribute to the induced hypertension in this experimental model.     

Reflex inhibition of heart rate and efferent cardiac sympathetic outflow induced by colorectal distension in anesthetized rats

Colorectal distensions of 60 and 80 mmHg significantly reduced heart rate (HR) and cardiac sympathetic nerve activity in anesthetized rats. This bradycardiac response was not influenced by the intravenous administration of atropine, but was abolished by propranolol, suggesting that it was elicited by sympathetic but not vagal efferent nerves.