The effects of indapamide on Vascular reactivity in experimental hypertension

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Abstract
Indapamide (13 mg to 16 mg/kg p.o.) produced a fall in blood pressure in conscious renal hypertensive cats without any reflex tachycardia. Repeated administration of indapamide for 2 weeks effected a well maintained reduction in blood pressure. Furthermore, the hypotensive effect of clonidine (20μg i.c.v.) was enhanced 1 week after completion of treatment with indapamide, suggesting a long-lasting effect of indapamide. In experimental hypertensive rats, indapamide (10 mg/kg p.o.) lowered blood pressure (40 mmHg) recorded directly from an in-dwelling catheter and the effect was maintained for 24 hours. In DOCA-saline hypertensive rats, 10-days' treatment with indapamide (10 mg/kg p.o.) or hydrochlorothiazide (5 mg/kg i.p.) produced falls in blood pressure of similar magnitude, as measured by an indirect method. Vasopressor effects induced by i.v. noradrenaline, 5-HT, tyramine or by stimulation of the entire sympathetic outflow were significantly reduced by indapamide pre-treatment but not by hydrochlorothiazide. Vascular reactivity of isolated rat mesentery preparations to noradrenaline, 5-HT and ATP was not reduced by indapamide pre-treatment but such treatment did reduce the frequency of spontaneous contractions in isolated rat portal vein preparations. The results suggest a vascular site of action for indapamide.