Central Depressor Action of Nitric Oxide Is Deficient in Genetic Hvpertension

Inhibition of NO synthase (NOS) in the central nervous system (CNSJ causes a pressor response: This observation indicates that NO is normally produced at a CNS site @ where it has a tonic blood pressure lowering effect. The current study tests the hypothesis &hat a deficient NOS activity in the CNS may contribute to the pressure eleva-tion in genetically hypertensive rats. NO adminis-tered intracerebroventricularly (ICV) caused a greater fall in mean arterial pressure (MAP; femo-ral artery) in hypertensive (SHRSP) than in nor-(motensive (WKYJ rats,-66.1 f 3.4 mm Hg u-23.7 i 3.9 mm Hg, respectively. Yet when endogenous NO was increased by stimulating NOS with ICV calcium, the depressor response was less in SHRSP than in WKY, 13.7 + 1.1 mm Hg u 26.7 f 19 mm Hg. Likewise, when NOS was blocked with N”‘-nitro+arginine methyl ester (L-NAME), the result-ant pressor response was less in SHRSP than in WKY,13.8 f: 1.1 mm Hg D 22.2 at 1.1 mm Hg. Block-ade of the action of cGMP, a mediator of the-&ion of NO, caused a pressor response c4 5o IC X.9 mm Hg and 22.6 f 8.7 mm Hg!I- ’ <.01) in the hyperten-sive and normotensive rats, respectively. I&&o-lytic ablation of the anteroventral third cerebral ventricle (A v’3VJ did not alter blood pressure re-sponses to NO or to agents that alter NOS activity. We conclude that a deficit in NOS a&&y in some other central cardiovascular regulatory area may contribute to tire elevated arterial pressure of these genetically hypertensive rats. Am J Hypertens 1996