THE CENTRAL EFFECTS OF A NITRIC-OXIDE SYNTHASE INHIBITOR (N-OMEGA-NITRO-L-ARGININE) ON BLOOD-PRESSURE AND PLASMA-RENIN

An endothelium-derived relaxing factor has been identified as nitric o xide ( NO ). Peripheral and central administration of nitric oxide syn thase inhibitors result in an increase in renal sympathetic nerve acti vity and an increase in blood pressure. The goal of our study was to d etermine if the increase in blood pressure following central NO syntha se inhibition with N(omega)-nitro-L-arginine (L-NNA) is caused by the release of renin. Six groups of Sprague-Dawley rats were used. Group I (control) received intracerebroventricular (i.c.v.) artificial cerebr ospinal fluid. Groups II & III received i.c.v. L-NNA, 5 & 15 mug / min . respectively. Group IV was treated with intravenous L-NNA, 15 mug / min. Group V, after bilateral nephrectomy, received i.c.v. L-NNA, 15 m ug / min. Group VI received i.c.v. L-arginine, 60 mug / min. and i.c.v . L-NNA, 15 mug / min., simultaneously. Plasma renin concentration was measured in groups I, III , IV & V. Mean arterial blood pressure was significantly increased in groups II , III & V, i.e., following i.c.v. infusion of L-NNA. The increase in mean arterial blood pressure was s ignificantly greater when the dose was increased from 5 to 15 mug / mi n. and it was eliminated when L-arginine was added to the infusion. Th e increase in blood pressure was attended by no change in heart rate. While the plasma renin concentration increased significantly in group III, this could not explain the increase in blood pressure since the n ephrectomized group (V) showed no increase in renin concentration but an equivalent increase in blood pressure. The results show that acute central administration of a low dose of L-NNA increases blood pressure in rats and this increase can be prevented by central administration of L-arginine. However, intravenous infusion of the same dose (15 mug/ min.) of L-NNA does not change blood pressure. We conclude that L-NNA acts directly within the central nervous system to increase blood pre ssure by a renin - independent mechanism. These results imply that cen tral nitric oxide plays an important role in the regulation of blood p ressure.