Vol. 275, Issue 6, R1950-R1957, December 1998
Antagonism of ANG II type 1 receptors protects the endothelium
during the early stages of renal hypertension in rats
Jin
Hoshino,
Tetsuya
Nakamura,
Toshiaki
Kurashina,
Yuichiro
Saito,
Hiroyuki
Sumino,
Zenpei
Ono,
Hironosuke
Sakamoto,
Keiko
Kowase, and
Ryozo
Nagai
The Second Department of Internal Medicine, Gunma University School
of Medicine, Maebashi, 371-8511 Japan
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.
acetylcholine; sodium nitroprusside; bradykinin
