Role of the central nervous system in the development of hypertension produced by chronic nitric oxide blockade in rats

We examined the role of the central nervous system, and particularly the re nin-angiotensin (RA) system, in the development of hypertension produced by chronic inhibition of NO synthesis. In experiment 1, Wistar rats drank eit her nitro-L-arginine methyl ester (L-NAME) or tap water. Before L-NAME trea tment rats were divided into 6 groups. Four of them were administered eithe r losartan or artificial cerebroventricular fluid (a-CSF) intracerebroventr icularly (i.c.v.) for 1 week using an osmotic mini pump. The other two grou ps were administered the same amount of losartan intravenously (i.v.). In e xperiment 2, cardiovascular responses to acute i.c.v. losartan and muscimol , a GABAA agonist, were examined in conscious L-NAME-treated rats. Finally, in experiment 3, effects of ablation of the AVIV (anteroventral third vent ricle) area, known to be one of the centers of cardiovascular control, were tested in the development of L-NAME hypertension. The development of hyper tension by L-NAME treatment was attenuated with chronic i.c.v. losartan in a dose-dependent manner, while i.v. losartan had no effect. One week after cessation of i.c.v, losartan, blood pressure was elevated to the same level as in a-CSF infused, L-NAME-treated rats. Acute i.c.v. losartan produced n o cardiovascular changes in either L-NAME-treated or control rats. On the o ther hand, although i.c.v. muscimol elicited depressor effects in both grou ps, these responses were significantly larger in L-NAME-treated rats. Cardi ovascular responses to i.v. hexamethonium were similar in both groups. The existence of prior lesions in the AV3V area significantly attenuated the de velopment of L-NAME-induced hypertension. These results indicate that the c entral RA system plays an important role in the development of hypertension produced by chronic inhibition of NO synthase, Moreover, disorder of the c entral GABA system, rather than that of the RA system, might be important i n the maintenance of hypertension in this model.