Central depressor action of nitric oxide is deficient in genetic hypertension.
Inhibition of NO synthase (NOS) in the central nervous system (CNS) causes a pressor response. This observation indicates that NO is normally produced at CNS site(s) where it has a tonic blood pressure lowering effect. The current study tests the hypothesis that a deficient NOS activity in the CNS may contribute to the pressure elevation in genetically hypertensive rats. NO administered intracerebroventricularly (ICV) caused a greater fall in mean arterial pressure (MAP; femoral artery) in hypertensive (SHRSP) than in normotensive (WKY) rats, -66.1 +/- 3.4 mm Hg v -23.7 +/- 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 v 26.7 +/- 1.9 mm Hg. Likewise, when NOS was blocked with N omega- nitro-L-arginine methyl ester (L-NAME), the resultant pressor response was less in SHRSP than in WKY, 13.8 +/- 1.1 mm Hg v 22.2 +/- 1.1 mm Hg. Blockade of the action of cGMP, a mediator of the action of NO, caused a pressor response of 6.0 +/- 2.8 mm Hg and 22.6 +/- 8.7 mm Hg (P < .01) in the hypertensive and normotensive rats, respectively. Electrolytic ablation of the anteroventral third cerebral ventricle (AV3V) did not alter blood pressure responses to NO or to agents that alter NOS activity. We conclude that a deficit in NOS activity in some other central cardiovascular regulatory area may contribute to the elevated arterial pressure of these genetically hypertensive rats.
Cabrera
C L
CL
University of Michigan, Ann Arbor 48109-0622, USA.
Bealer
S L
SL
Bohr
D F
DF
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D004333:Drug Administration Routes; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology*; D007276:Injections, Intraventricular; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester