Nitric oxide (NO) in the nucleus tractus solitarii (NTS) plays an important role in regulating sympathetic nerve activity. The aims of this study were to determine whether the activation of N-methyl-D-aspartate (NMDA) receptors in the NTS facilitates the release of L-glutamate (Glu) via NO production, and, if so, to determine whether this mechanism is involved in the depressor and bradycardic responses evoked by NMDA. We measured the production of NO in the NTS as NO2- and NO3- (NO(x)) or Glu levels by in vivo microdialysis before, during, and after infusion of NMDA in anesthetized rats. We also examined effects of N(omega)-nitro-L-arginine methyl ester (L-NAME) on the changes in these levels. NMDA elicited depressor and bradycardic responses and increased the levels of NO(x) and Glu. L-NAME abolished the increases in the levels of NO(x) and Glu and attenuated cardiovascular responses evoked by NMDA. These results suggest that NMDA receptor activation in the NTS induces Glu release through NO synthesis and that Glu released via NO enhances depressor and bradycardic responses.

The aims of this study were to determine 1) whether endothelin (ET)-1 affects the neuronal activity of the NTS neurons, 2) whether specific ET receptor antagonists affect the neuronal activity of the NTS neurons, and 3) whether ET-1 or ET receptor antagonists modulate the responses of the nucleus of the solitary tract (NTS) neurons to l-glutamate (Glu). The single-unit discharge was extracellularly recorded with a fine electrode from medulla brain slice preparations of rats. ET-1 and Glu were iontophoretically applied to the recorded neuron. Both ET-1 and Glu increased the neuronal activity. The ETA receptor antagonist BQ-123 attenuated the basal neuronal activity. ET-1 augmented the magnitude of the increases in the neuronal activity evoked by Glu, and these responses were antagonized by BQ-123. These studies suggest the following conclusions: 1) ET-1 increases the neuronal activity of the NTS neurons via ETA receptors, 2) endogenous ET plays a controlling role of the neuronal activity of NTS neurons, and 3) ET-1 augments the responses evoked by Glu, believed to be the neurotransmitter from the solitary tract, via ETA receptors. These results suggest that ET-1 facilitates synaptic transmission in the NTS.

It has been shown that nitric oxide in the brain stem plays an important role in the control of sympathetic nerve activity. We examined the role of endogenous nitric oxide in the brain stem in the rapid central adaptation of baroreflex control of sympathetic nerve activity in anesthetized rabbits. Bilateral carotid sinuses were isolated, and a stepwise increase in pressure of 25 or 50 mm Hg for 50 to 60 seconds was applied to the carotid sinuses while the arterial pressure and renal sympathetic nerve activity were recorded. The renal sympathetic nerve activity was inhibited by the stepwise increase in carotid sinus pressure, but thereafter it gradually returned toward the baseline level despite the fact that carotid sinus pressure was kept constant. This procedure was performed after intracisternal injection of N(omega)-nitro-L-arginine methyl ester (L-NAME, 8 micromol), N(omega)-nitro-D-arginine methyl ester (D-NAME, 8 micromol), L-arginine (40 micromol), or the vehicle solution. The magnitude of the immediate and maximal inhibition of renal sympathetic nerve activity caused by a stepwise increase in carotid sinus pressure was similar between the vehicle and L-NAME treatment, but the rate of recovery of the renal sympathetic nerve activity after immediate inhibition was faster after L-NAME than after vehicle. L-Arginine reversed the effects of L-NAME. However, D-NAME or L-arginine alone had no such effects on the rate of recovery of the nerve activity. These results thus suggest that endogenous nitric oxide in the brain stem attenuates rapid adaptation of the arterial baroreflex control of the sympathetic nerve activity in rabbits.

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Recent studies have suggested that the central nervous system is responsible for activation of sympathetic nerve activity (SNA) and the renin-angiotensin system in heart failure (HF). The aim of this study was to determine whether activation of the renin-angiotensin system within the nucleus of the solitary tract (NTS) plays a role in enhanced SNA in HF. High-output HF was induced by an aortocaval (A-V) shunt with some modifications in the rat. These rats exhibited a left ventricular dilatation and hemodynamic signs of high-output HF. Urinary catecholamine excretion and maximal renal SNA (RSNA) were greater in the A-V shunted rats than in the control rats. Microinjection of an angiotensin II type 1-receptor antagonist, CV11974, into the NTS was performed. The arterial pressure and RSNA were reduced by CV11974 to a greater degree in the A-V shunted rats than in the control rats. The expression of angiotensin-converting enzyme mRNA in the medulla was greater in the A-V shunted rats than in the control rats. These results suggest that activation of the renin-angiotensin system within the NTS contributes to an enhanced SNA in this model.