Exaggerated vascular response due to endothelial dysfunction and role of the renin-angiotensin system at early stage of renal hypertension in rats.
We investigated whether endothelial dysfunction might contribute to the exaggerated vasoconstriction that was induced by the administration of norepinephrine at the early stage of one-kidney, one-clip renal hypertension (1K1C) in rats. We also studied the role of the renin-angiotension system in this phenomenon. Male Wistar rats were killed 48 hours after the induction of renal artery stenosis or sham operation, and ring preparations of the thoracic aorta were obtained. The isometric contraction and relaxation of aortic strips produced by norepinephrine and acetylcholine, respectively, were recorded with a force-displacement transducer. The aorta of 1K1C rats showed a significantly (P < .05) exaggerated contractile response to norepinephrine as compared with that of control rats. Rubbing the endothelium and treatment with methylene blue or NG-monomethyl L-arginine acetate augmented the contractile responses to norepinephrine to a greater extent in control rats than in 1K1C rats; therefore, the responses of the groups did not differ significantly. In the second experiment, rats received 0.05% captopril, 0.02% enalapril, or 0.02% nicardipine in the drinking water for 1 day before and for 48 hours after the induction of renal artery stenosis or sham operation. The increased contractile responses of the aorta to norepinephrine in 1K1C rats were normalized to the level of the control rats by treatment with either captopril or enalapril but not with nicardipine. These results suggest that the endothelial dysfunction may contribute to the exaggerated norepinephrine-induced vasoconstriction observed in the 1K1C rats and that angiotensin I-converting enzyme inhibitors can restore the endothelial function.
Hoshino
J
J
Second Department of Internal Medicine, Gunma University School of Medicine, Maebashi, Japan.
Sakamaki
T
T
Nakamura
T
T
Kobayashi
M
M
Kato
M
M
Sakamoto
H
H
Kurashina
T
T
Yagi
A
A
Sato
K
K
Ono
Z
Z
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006977:Hypertension, Renal / Q000503:physiopathology*; D008297:Male; D009529:Nicardipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012084:Renin-Angiotensin System / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation
D009529:Nicardipine; D000109:Acetylcholine; D009638:Norepinephrine