Nitric oxide modulation of glutamatergic, baroreflex, and cardiopulmonary transmission in the nucleus of the solitary tract

Abstract

The neuromodulatory effect of NO on glutamatergic transmission has been studied in several brain areas. Our previous single-cell studies suggested that NO facilitates glutamatergic transmission in the nucleus of the solitary tract (NTS). In this study, we examined the effect of the nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) on glutamatergic and reflex transmission in the NTS. We measured mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) from Inactin-anesthetized Sprague-Dawley rats. Bilateral microinjections of L-NAME (10 nmol/100 nl) into the NTS did not cause significant changes in basal MAP, HR, or RSNA. Unilateral microinjection of (RS)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA, 1 pmol/100 nl) into the NTS decreased MAP and RSNA. Fifteen minutes after L-NAME microinjections, AMPA-evoked cardiovascular changes were significantly reduced. N-methyl-D-aspartate (NMDA, 0.5 pmol/100 nl) microinjection into the NTS decreased MAP, HR, and RSNA. NMDA-evoked falls in MAP, HR, and RSNA were significantly reduced 30 min after L-NAME. To examine baroreceptor and cardiopulmonary reflex function, L-NAME was microinjected at multiple sites within the rostro-caudal extent of the NTS. Baroreflex function was tested with phenylephrine (PE, 25 microg iv) before and after L-NAME. Five minutes after L-NAME the decrease in RSNA caused by PE was significantly reduced. To examine cardiopulmonary reflex function, phenylbiguanide (PBG, 8 microg/kg) was injected into the right atrium. PBG-evoked hypotension, bradycardia, and RSNA reduction were significantly attenuated 5 min after L-NAME. Our results indicate that inhibition of NOS within the NTS attenuates baro- and cardiopulmonary reflexes, suggesting that NO plays a physiologically significant neuromodulatory role in cardiovascular regulation.

Altered nitroxidergic and NMDA receptor-mediated modulation of baroreflex-mediated heart rate in obese Zucker rats

“…A previous study indicated that the inhibition of nitric oxide synthase within the nucleus tractus solitarii attenuated baroreflex, suggesting that NO might have a physiologically significant neuromodulatory role in baroreflex regulation. 24 In this study, the baroreflex-mediated bradycardia was remarkably reduced by intravenous infusion of L-NAME in lean rats but not in obese Zucker rats. The findings based on the effects of nitric oxide synthase inhibitor in lean and obese Zucker rats implied that NO-mediated baroreflex bradycardia was normally modulated by endogenous NO in lean rats, …”

“…31 The release of NO facilitates glutamatergic transmission in the brain or NTS and induces NMDA receptor activation. 24,31 The interaction of glutamatergic and nitroxidergic modulation regulates baroreflex-mediated heart rate. 24,31 In this study, the blunted BRS in obesity was significantly blocked to nearly no BRS after administration of both DXM and L-NAME.…”

“…24,31 The interaction of glutamatergic and nitroxidergic modulation regulates baroreflex-mediated heart rate. 24,31 In this study, the blunted BRS in obesity was significantly blocked to nearly no BRS after administration of both DXM and L-NAME. The findings suggest that the blunted BRS in obesity was mediated by the coeffects of NO and NMDA.…”

“…25 A previous study suggested that nitric oxide (NO) has a physiologically significant neuromodulatory role in baroreflex regulation. 24 Adult obese Zucker rats have elevated sympathetic vasomotor tone and arterial pressure and blunted sympathetic baroreceptor reflexes compared with adult lean Zucker rats. 13 Our previous studies indicate that altered glutamatergic mechanisms exerting an effect on NMDA receptors, as well as nitroxidergic mechanisms, are partially responsible for blunted chemoresponses in obese Zucker rats.…”

“…22 The neuromodulatory effect of nitroxidergic and glutamatergic transmission has been reported to be involved in baroreflex regulation. [23][24] The N-methyl-D-aspartate (NMDA)-mediated mechanism has an important role in the mechanism of baroreflex. 23 The gain of baroreflex bradycardia is reduced by the microinjection of NMDA receptor antagonists.…”