NITRIC-OXIDE WITHIN THE PARAVENTRICULAR NUCLEUS MEDIATES CHANGES IN RENAL SYMPATHETIC-NERVE ACTIVITY

The paraventricular nucleus (PVN) of the hypothalamus is known to be i nvolved in the control of sympathetic outflow. The goal of the present study was to examine the role of nitric oxide within the PVN in the r egulation of renal sympathetic nerve activity. Renal sympathetic nerve discharge (RSND), arterial blood pressure, and heart rate in response to the microinjection of nitric oxide synthase inhibitor N-G-monometh yl-L-arginine (L-NMMA; 50, 100, and 200 pmol) into the PVN were measur ed in male Sprague-Dawley rats. Microinjection of L-NMMA elicited an i ncrease in RSND, arterial blood pressure, and heart rate. Administrati on of N-G-monomethyl-D-arginine (n-NMMA, 50-200 pmol) into the PVN did not change RSND, arterial pressure, or heart rate. Similarly, microin jection of another nitric oxide inhibitor N-G-nitro-L-arginine methyl ester (L-NAME; 100 nmol) also elicited an increase in RSND, arterial b lood pressure, and heart rate. L-Arginine (100 nmol) reversed the effe cts of L-NAME in the PVN. Furthermore, microinjection of sodium nitrop russide (SNP; 50, 100, and 200 nmol) into the PVN elicited a significa nt decrease in RSND, arterial blood pressure, and heart rate. These ef fects of L-NMMA, L-NAME, and SNP on RSND and arterial blood pressure w ere not mediated by their vasoactive action because microinjection of phenylephrine and hydralazine did not elicit similar respective change s. In conclusion, our data indicate that endogenous nitric oxide withi n the PVN regulates sympathetic outflow via some inhibitory mechanisms . Altered nitric oxide mechanisms within the PVN may contribute to ele vated sympathetic nerve activity observed during various disease state s such as heart failure and hypertension.