The nucleus tractus solitarii (NTS) receives afferent projections from the arterial baroreceptors, carotid chemoreceptors and cardiopulmonary receptors and as a function of this information produces autonomic adjustments in order to maintain arterial blood pressure within a narrow range of variation. The activation of each of these cardiovascular afferents produces a specific autonomic response by the excitation of neuronal projections from the NTS to the ventrolateral areas of the medulla (nucleus ambiguus, caudal and rostral ventrolateral medulla). The neurotransmitters at the NTS level as well as the excitatory amino acid (EAA) receptors involved in the processing of the autonomic responses in the NTS, although extensively studied, remain to be completely elucidated. In the present review we discuss the role of the EAA L-glutamate and its different receptor subtypes in the processing of the cardiovascular reflexes in the NTS. The data presented in this review related to the neurotransmission in the NTS are based on experimental evidence obtained in our laboratory in unanesthetized rats. The two major conclusions of the present review are that a) the excitation of the cardiovagal component by cardiovascular reflex activation (chemo-and Bezold-Jarisch reflexes) or by L-glutamate microinjection into the NTS is mediated by N-methyl-D-aspartate (NMDA) receptors, and b) the sympatho-excitatory component of the chemoreflex and the pressor response to L-glutamate microinjected into the NTS are not affected by an NMDA receptor antagonist, suggesting that the sympatho-excitatory component of these responses is mediated by non-NMDA receptors.

Our previous studies have shown that stimulation of the anteroventral third ventricle (AV3V) region of the brain increases atrial natriuretic peptide (ANP) release, whereas lesions of the AV3V region or median eminence of the tuber cinereum block the release of ANP caused by blood volume expansion. These results suggest that participation of the central nervous system is critical to this response. The role of baroreceptors in the response was evaluated in the current research by studying the response of plasma ANP to blood volume expansion induced by intravenous injection of hypertonic saline solution (0.3 M NaCl, 2 ml/100 g of body weight, over 1 min) in conscious, freely moving male rats. Plasma samples were assayed for ANP by radioimmunoassay. In sham-operated rats, blood volume expansion induced a rapid increase in plasma ANP: the concentration peaked at 5min and remained elevated at 15 min after saline injection. One week after deafferentation of the carotid-aortic baroreceptors, basal plasma ANP concentrations were highly significantly decreased on comparison with values of sham-operated rats; plasma ANP levels S min after blood volume expansion in the deafferented rats were greatly reduced. Unilateral right vagotomy reduced resting levels of plasma ANP but not the response to blood volume expansion; resting concentrations of plasma ANP and responses to expansion were normal in bilaterally vagotomized rats. In rats that had undergone renal deafferentation, resting levels of ANP were normal but the response to blood volume expansion was significantly suppressed. The evidence indicates that afferent impulses via the right vagus nerve may be important under basal conditions, but they are not required for the ANP release induced by blood volume expansion. In contrast, baroreceptor impulses from the carotid-aortic sinus regions and the kidney are important pathways involved in the neuroendocrine control of ANP release. The evidence from these experiments and our previous stimulation and lesion studies indicates that the ANP release in response to volume expansion is mediated by afferent baroreceptor input to the AV3V region, which mediates the increased ANP release via activation of the hypothalamic ANP neuronal system. Atrial natriuretic peptide (ANP), which is primarily localized to the atrial myocytes, plays an important role in control of body fluid homeostasis by decreasing salt and water intake and increasing salt and water excretion (1-7). When the blood volume is expanded-for example, by intravenous injection of saline solution-ANP is released into the circulation and induces natriuresis, in part by direct action on the kidneys (8, 9). Natriuresis is also promoted by direct suppression of the release of aldosterone from the adrenal glomerulosa by ANP (1). ANP also inhibits the release of renin from the juxtaglomerular apparatus of the kidneys (10, 11), which decreases the release of angiotensin II, further decreasing the release of aldosterone. Since angiotensin II is an important mediator of sa...

Activity in vagal preganglionic motoneurones running to the heart provokes a generalized cardioinhibition producing a decrease not only in heart rate (chronotropy), but also in the rate of atrioventricular (AV) conduction (dromotropy), and in the force of myocardial contraction (inotropy). These effects are secondary to, and are contingent upon, excitation of ganglion cells located in clusters on the epicardium of the dorsum of the atria, closely apposed to the sites of entry of the major veins. There is evidence that in many of the larger mammalian species, the ganglion cells are clustered into discrete zones or 'fat pads' which project to different regions of the heart and selectively control cardiac function (Ardell & Randall, 1986; Randall et al. 1986a,b;Gatti et al. 1995Gatti et al. , 1997. Several recent studies have described the anatomy of the cardiac vagal ganglia in the rat (Pardini et al. 1987;Abrahamian et al. 1991;Klimaschewski et al. 1992;Burkholder et al. 1992;deSouza et al. 1996;Cheng et al. 1999;Cheng & Powley, 2000).Although the results of some of these studies suggest the existence of a functional topography (e.g. Pardini et al. 1987), there is little clear physiological or pharmacological evidence of this in the rat. In the only previous study of a possible functional organization of rat cardiac ganglia (Burkholder et al. 1992), a brief description is given of a partial selectivity revealed by differing responses to vagal stimulation following local infiltration of hexamethonium into identified fat pads.Data from preliminary experiments in this laboratory suggest that glutamate excitation of cardiac vagal preganglionic motoneurones from different regions of the rat nucleus ambiguus results in differential chronotropic and dromotropic effects (Sampaio et al. 2000). That this may result from a different termination pattern of preganglionic axons onto ganglion cells from different ganglionic clusters is supported by the finding of restricted ganglionic innervation from motoneurones labelled with anterograde Vagal cardioinhibition is exerted through a reduction not only in the heart rate but also in the rate of propagation of the cardiac action potential and in myocardial contractility. In several species, such effects can be produced independently by selective activation of ganglia in identified 'fat pads'. In this study we investigate differential control of heart rate and atrioventricular conduction by two ganglionic clusters in the rat, a species increasingly important in studies of cardiovascular control. Epicardial sites producing low-threshold changes in P-P and P-R interval of the ECG in an arterially perfused preparation were explored with concentric bipolar stimulating electrodes. Stimulation sites centred on two principal ganglia, the sinoatrial (SA) ganglion at the junction of the right superior vena cava and right atrium, and the atrioventricular (AV) ganglion at the junction of the inferior pulmonary veins and left atrium. Stimulation of the SA ganglion decreased heart rate in all ...

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The maintenance of arterial pressure at levels adequate to perfuse the tissues is a basic requirement for the constancy of the internal environment and survival. The objective of the present review was to provide information about the basic reflex mechanisms that are responsible for the moment-to-moment regulation of the cardiovascular system. We demonstrate that this control is largely provided by the action of arterial and non-arterial reflexes that detect and correct changes in arterial pressure (baroreflex), blood volume or chemical composition (mechanoand chemosensitive cardiopulmonary reflexes), and changes in bloodgas composition (chemoreceptor reflex). The importance of the integration of these cardiovascular reflexes is well understood and it is clear that processing mainly occurs in the nucleus tractus solitarii, although the mechanism is poorly understood. There are several indications that the interactions of baroreflex, chemoreflex and Bezold-Jarisch reflex inputs, and the central nervous system control the activity of autonomic preganglionic neurons through parallel afferent and efferent pathways to achieve cardiovascular homeostasis. It is surprising that so little appears in the literature about the integration of these neural reflexes in cardiovascular function. Thus, our purpose was to review the interplay between peripheral neural reflex mechanisms of arterial blood pressure and blood volume regulation in physiological and pathophysiological states. Special emphasis is placed on the experimental model of arterial hypertension induced by N-nitro-L-arginine methyl ester (L-NAME) in which the interplay of these three reflexes is demonstrable.

The contribution of alpha(2)-receptor mechanisms in the rostral ventrolateral medulla (RVLM) in mediating the enhanced renal excretory responses evoked by the intravenous infusion of the alpha(2)-receptor agonist xylazine was examined in ketamine-anesthetized rats. In ketamine-anesthetized rats, the bilateral microinjection of the alpha(2)-receptor antagonist yohimbine into the RVLM significantly reduced the enhanced levels of urine flow rate (V) and urinary sodium excretion (UNaV) produced by xylazine. In contrast, microinjection of yohimbine into the RVLM of chronically bilaterally renal-denervated rats significantly reduced the xylazine-evoked diuretic, but not natriuretic, response. In separate ketamine-anesthetized rats, intravenous xylazine infusion produced a near complete inhibition of renal sympathetic nerve activity (RSNA). The subsequent microinjection of yohimbine into the RVLM reversed this neural response and concurrently decreased V and UNaV. Together, these results indicate that during intravenous infusion, xylazine activates alpha(2)-receptor mechanisms in the RVLM to selectively promote urinary sodium excretion by a renal nerve-dependent pathway. In contrast, activation of alpha(2)-receptor in the RVLM affects the renal handling of water by a pathway independent of the renal nerves. This latter pathway may involve an interaction with other brain regions involved in antidiuretic hormone release (e.g., paraventricular nucleus of the hypothalamus).

Experimental studies show that the unsaturated high-fat diet-induced obesity promotes vascular alterations characterized by improving the endothelial L-arginine/Nitric Oxide (NO) pathway. Leptin seems to be involved in this process, promoting vasodilation via increasing NO bioavailability. The aim of this study was to test the hypothesis that unsaturated high-fat diet-induced obesity does not generate endothelial dysfunction via increasing the vascular leptin/Akt/eNOS signaling. Thirty-day-old male Wistar rats were randomized into two groups: control (C) and obese (Ob). Group C was fed a standard diet, while group Ob was fed an unsaturated high-fat diet for 27 weeks. Adiposity, hormonal and biochemical parameters, and systolic blood pressure were observed. Concentration response curves were performed for leptin or acetylcholine in the presence or absence of Akt and NOS inhibitor. Our results showed that an unsaturated high-fat diet promoted a greater feed efficiency (FE), elevation of body weight and body fat (BF), and an adiposity index, characterizing a model of obesity. However, comorbidities frequently associated with experimental obesity were not visualized, such as glucose intolerance, dyslipidemia and hypertension. The evaluation of the endothelium-dependent relaxation with acetylcholine showed no differences between the C and Ob rats. After NOS inhibition, the response was completely abolished in the Ob group, but not in the C group. Furthermore, Akt inhibition completely blunted vascular relaxation in the C group, but not in the Ob group, which was more sensitive to leptin-induced vascular relaxation. L-NAME incubation abolished the relaxation in both groups at the same level. Although Akt inhibitor pre-incubation reduced the leptin response, group C was more sensitive to its effect. In conclusion, the high-unsaturated fat diet-induced obesity improved the vascular reactivity to leptin and does not generate endothelial dysfunction, possibly by the increase in the vascular sensitivity to leptin and increasing NO bioavailability. Moreover, our results suggest that the increase in NO production occurs through the increase in NOS activation by leptin and is partially mediated by the Akt pathway.

Earlier studies report that sinoaortic baroreceptor denervation (SAD) in rats causes moderate elevation of mean arterial pressure along with a marked increase of arterial pressure lability (APL). In this context, we studied the effects of selective aortic denervation (AD) or selective carotid denervation (CD) on the regulation of blood pressure. In addition, we evaluated the effects of selective or total baroreceptor denervation on pulmonary ventilation and ventilationrelated changes of arterial pressure. Mean arterial pressure was evaluated by computerassisted techniques, and ventilation was measured by whole body plethysmography on conscious freely moving rats. With this approach, equal increases of mean arterial pressure were obtained for rats that had undergone AD, CD, and SAD. The APL was higher in SAD rats than in selectively denervated rats. CD and AD rats had an elevated APL relative to sham-operated animals, and its increase was approximately equal for the two selectively denervated groups. Total as well as selective denervation had relatively small effects on ventilation and on the general pattern of breathing. In all groups, this pattern consisted of regular ventilation, periodically interrupted by single deeper breaths. In SAD, AD, and CD animals, these larger tidal volumes were associated with marked transient reductions of mean arterial pressure, whereas small decreases of pressure occurred in sham-operated rats. The results indicate that both groups of baroreceptors must be present to keep mean arterial pressure at its normal level. Moreover, both receptor groups are equally important in reducing APL. Ventilation contributes to generation of APL after total or selective baroreceptor removal. Such ventilation-induced pressure changes are kept at a minimum in baroreceptor-intact rats.