Role of ANG II in hypertension produced by chronic inhibition of nitric oxide synthase in conscious rats.
These experiments tested the hypothesis that hypertension caused by chronic inhibition of nitiric oxide synthase (NOS) is associated with augmented pressor responsiveness to angiotensin II (ANG II). Antagonism of ANG II AT1 receptors with losartan caused a greater fall in blood pressure (BP) in rats treated for 2 wk with the NOS inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) than in normotensive rats. The delayed time course of the decline in BP implicated the slow pressor effect (SPE) of ANG II in L-NAME hypertension. Further experiments showed that direct elicitation of the SPE by continuous low-dose (4 ng/min) intravenous infusion of ANG II in enalapril-treated rats resulted in a larger chronic increase in BP if NOS was inhibited. However, L-NAME alone also caused a significant increase in BP in enalapril-treated rats. The combined effect on BP of ANG II and L-NAME was merely additive. These results confirm that ANG II is involved in L-NAME hypertension. However, chronic pressor responsiveness to the peptide is not augmented by L-NAME.
Melaragno
M G
MG
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824-1317, USA.
Fink
G D
GD
D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004656:Enalapril / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013777:Tetrazoles / Q000494:pharmacology; D013997:Time Factors
D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D004656:Enalapril; D019001:Nitric Oxide Synthase; D019808:Losartan; D019331:NG-Nitroarginine Methyl Ester