EXAGGERATED VASCULAR-RESPONSE DUE TO ENDOTHELIAL DYSFUNCTION AND ROLEOF THE RENIN-ANGIOTENSIN SYSTEM AT EARLY-STAGE OF RENAL-HYPERTENSION IN RATS

We investigated whether endothelial dysfunction might contribute to th e exaggerated vasoconstriction that was induced by the administration of norepinephrine at the early stage of one-kidney, one-clip renal hyp ertension (1K1C) in rats. We also studied the role of the renin-angiot ensin system in this phenomenon. Male Wistar rats were killed 48 hours after the induction of renal artery stenosis or sham operation, and r ing preparations of the thoracic aorta were obtained. The isometric co ntraction and relaxation of aortic strips produced by norepinephrine a nd acetylcholine, respectively, were recorded with a force-displacemen t transducer. The aorta of 1K1C rats showed a significantly (P < .05) exaggerated contractile response to norepinephrine as compared with th at of control rats. Rubbing the endothelium and treatment with methyle ne blue or NG-monomethyl L-arginine acetate augmented the contractile responses to norepinephrine to a greater extent in control rats than i n 1K1C rats; therefore, the responses of the groups did not differ sig nificantly. In the second experiment, rats received 0.05% captopril, 0 .02% enalapril, or 0.02% nicardipine in the drinking water for 1 day b efore and for 48 hours after the induction of renal artery stenosis or sham operation. The increased contractile responses of the aorta to n orepinephrine in 1K1C rats were normalized to the level of the control rats by treatment with either captopril or enalapril but not with nic ardipine. These results suggest that the endothelial dysfunction may c ontribute to the exaggerated norepinephrine-induced vasoconstriction o bserved in the 1K1C rats and that angiotensin I-converting enzyme inhi bitors can restore the endothelial function.