Direct Vascular Actions of Indapamide in Aorta from Renal Hypertensive Rats

Purpose: Thiazide diuretics exert their hypotensive efficacy through a combined vasodilator and diuretic effect. The present study was conducted to assess the inhibitory effect of thiazide diuretic, hydrochlorothiazide, and the thiazide-like diuretics, indapamide and chlorthalidone on contractile responses to norepinephrine and arginine vasopressin in aortic rings from 2K1C renal hypertensive and sham-clipped normotensive rats. Methods: 2K1C hypertension was made by clipping the left renal artery and age-matched control rats received a sham treatment. Changes in the tension of aortic ring preparations were measured isometrically. Results: Indapamide inhibits the contractile responses to norepinephrine and vasopressin in aortic rings from 2K1C rats, while it did not modify in control rats. The inhibitory effect of indapamide was abolished by endothelium removal. Hydrochlorothiazide or chlorthalidone did not affect the vasoconstriction induced by norepinephrine and vasopressin either in sham or in 2K1C hypertensive rats. Conclusion: These results suggest that indapamide inhibits the contractile responses to norepinephrine and vasopressin via an endothelium-dependent mechanism in 2K1C renal hypertension.