The central effects of a nitric oxide synthase inhibitor (N omega-nitro-L-arginine) on blood pressure and plasma renin.

Abstract

An endothelium-derived relaxing factor has been identified as nitric oxide (NO). Peripheral and central administration of nitric oxide synthase inhibitors result in an increase in renal sympathetic nerve activity and an increase in blood pressure. The goal of our study was to determine if the increase in blood pressure following central NO synthase 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 cerebrospinal fluid. Groups II & III received i.c.v. L-NNA, 5 & 15 micrograms/min. respectively. Group IV was treated with intravenous L-NNA, 15 micrograms/min. Group V, after bilateral nephrectomy, received i.c.v. L-NNA, 15 micrograms/min. Group VI received i.c.v. L-arginine, 60 micrograms/min. and i.c.v. L-NNA, 15 micrograms/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 significantly greater when the dose was increased from 5 to 15 micrograms/min. and it was eliminated when L-arginine was added to the infusion. The 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 nephrectomized 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 micrograms/min.) of L-NNA does not change blood pressure. We conclude that L-NNA acts directly within the central nervous system to increase blood pressure by a renin-independent mechanism. These results imply that central nitric oxide plays an important role in the regulation of blood pressure.