EFFECT OF NITRIC-OXIDE WITHIN THE PARAVENTRICULAR NUCLEUS ON RENAL SYMPATHETIC-NERVE DISCHARGE - ROLE OF GABA

Both nitric oxide (NO) and GABA are known to provide inhibitory inputs to the paraventricular nucleus (PVN) of the hypothalamus and are invo lved in the control of sympathetic outflow. The purpose of the present study was to examine the interaction of NO and GABA in the regulation of renal sympathetic nerve activity in rats. The responses of renal n erve activity, blood pressure, and heart rate to microinjection of sod ium nitroprusside (SNP), an NO donor into the PVN were measured in the presence and absence of blockade of the GABA system (bicuculline; 2 n mol). Microinjection of SNP (50, 100, and 200 nmol) into the PVN elici ted significant decreases in renal nerve discharge, arterial blood pre ssure, and heart rate, reaching -36.4 +/- 9.7%, -11 +/- 5 mmHg, and -3 4 +/- 14 beats/min, respectively, at the highest dose. These responses were eliminated by blockade of the GABA system. Conversely, microinje ction of N-omega-nitro-L-arginine methyl ester (L-NAME; 50, 100, and 2 00 nmol) elicited significant increases in the renal sympathetic nerve discharge, arterial blood pressure, and heart rate, reaching 88.9 +/- 16.6%, 9 +/- 1 mmHg, and 29 +/- 9 beats/min, respectively, at the hig hest dose. These sympathoexcitatory responses were masked by prior blo ckade of the GABA system with bicuculline. The sympathoexcitatory effe ct of L-NAME was also eliminated by activation of the GABA system with muscimol. In conclusion, our data indicate that the inhibitory effect of endogenous NO within the PVN on the renal sympathetic nerve activi ty is mediated by GABA.