Angiotensin-(1-7) and nitric oxide interaction in renovascular hypertension.
New studies suggest that vasodilator systems may play an important role in restraining the rise in peripheral vascular resistance associated with the evolution of arterial hypertension. We characterized in conscious dogs the hemodynamic and hormonal effects of 4 weeks of feeding either the nitric oxide synthase inhibitor N omega-nitro-L-arginine (3 mg.kg-1.d-1) or the nitric oxide precursor L-arginine (0.3 mg.kg-1.d-1) during the evolution of two-kidney, one clip hypertension. Inhibition of nitric oxide production elicited a form of hypertension more severe than that produced in placebo-fed two-kidney, one clip dogs. The higher levels of blood pressure were accompanied by lower levels of plasma renin activity and lower angiotensin II concentrations. During the chronic phase of renovascular hypertension, the fall in blood pressure produced by acute systemic injections of lisinopril or losartan was significantly reduced in dogs given the nitric oxide inhibitor. In contrast, chronic administration of L-arginine had no effect on the magnitude of hypertension or on the increases in renin activity and hyperangiotensinemia associated with the evolution of renal hypertension. Likewise, the fall in blood pressure produced by pharmacological blockade of angiotensin II was not different from that recorded in untreated renal hypertensive dogs. The vasodilator component of the blood pressure response due to intravenous injections of angiotensin-(1-7) (1 to 100 nmol/kg) was augmented in both untreated and L-arginine-treated two-kidney, one clip hypertensive dogs, but was significantly attenuated in hypertensive dogs fed the nitric oxide synthase inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)
Nakamoto
H
H
Hypertension Center, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC 27157-1032, USA.
Ferrario
C M
CM
Fuller
S B
SB
Robaczewski
D L
DL
Winicov
E
E
Dean
R H
RH
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000803:Angiotensin I; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000809:Angiotensins / Q000097:blood; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects; D006978:Hypertension, Renovascular / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology; D017706:Lisinopril / Q000494:pharmacology; D019808:Losartan; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D010446:Peptide Fragments / Q000494:pharmacology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology
D000809:Angiotensins; D001713:Biphenyl Compounds; D007093:Imidazoles; D010446:Peptide Fragments; D013777:Tetrazoles; D000804:Angiotensin II; D019335:Nitroarginine; D009569:Nitric Oxide; D000803:Angiotensin I; D001120:Arginine; D017706:Lisinopril; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D007703:Peptidyl-Dipeptidase A; C118790:angiotensin I (1-7); D019808:Losartan