Antagonism of ANG II type 1 receptors protects the endothelium during the early stages of renal hypertension in rats.
The degree of involvement of the renin-angiotensin system in endothelial dysfunction was investigated by using a one-kidney, one-clip (1K,1C) model of renal hypertension. Male Wistar rats received 0.02% enalapril, 0.02% losartan, or tap water for 1 day before and for 48 h after the induction of renal artery stenosis or sham operation. The aorta of 1K,1C rats showed increased contraction and decreased relaxation responses produced by norepinephrine and acetylcholine, respectively, vs. control responses. Exposure to 10(-5) mol/l NG-monomethyl-L-arginine acetate augmented the contractile responses to norepinephrine to a greater extent in control rats than in the 1K,1C rats. The increased contraction and decreased relaxation responses to these agonists in the 1K,1C rats were normalized by enalapril or losartan. The addition of HOE-140 to the bath did not alter these normalized responses. Results suggest that angiotensin II causes endothelial dysfunction and reduces nitric oxide levels in 1K,1C rats. Such endothelial dysfunction enhanced the norepinephrine-induced contraction during the early-stage hypertension in 1K,1C rats.
Hoshino
J
J
The Second Department of Internal Medicine, Gunma University School of Medicine, Maebashi, 371-8511 Japan.
Nakamura
T
T
Kurashina
T
T
Saito
Y
Y
Sumino
H
H
Ono
Z
Z
Sakamoto
H
H
Kowase
K
K
Nagai
R
R
D000109:Acetylcholine / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D006977:Hypertension, Renal / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D014666:Vasomotor System / Q000503:physiopathology
D000319:Adrenergic beta-Antagonists; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D065168:Bradykinin Receptor Antagonists; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C065679:icatibant; D000109:Acetylcholine; D001920:Bradykinin; D009638:Norepinephrine