Changes in vascular reactivity in experimental hypertensive animals following treatment with indapamide

Indapamide at doses of 8–16 mg kg−1 day−1, orally, lowered arterial blood pressure (9–26 mm Hg) in conscious renal hypertensive cats during a two week treatment period. The antihypertensive effect was sustained for 5–7 h after dosing and was not accompanied by reflex tachycardia. Antihypertensive responses to injection of clonidine (20 μg, i.c.v.) were significantly enhanced one week after the completion of indapamide treatment but had returned to normal two weeks later. In DOCA/saline hypertensive rats, administration of indapamide 10 mg kg−1 day−1, orally, or hydrochlorothiazide, 5 mg kg−1 day−1, intraperitoneally, for 10 days produced similar falls in blood pressure (40–45 mm Hg) as measured by an indirect method. Pressor responses to intravenous noradrenaline or tyramine or electrical stimulation of the sympathetic outflow in the pithed rat preparation were much reduced by pretreatment with indapamide (10 mg kg−1, orally) for 10 days. However, cardiovascular reactivity was unaffected by hydrochlorothiazide pretreatment (5 mg kg−1 day−1, i.p.). Isolated perfused mesenteric artery***/preparations from indapamide-treated rats showed no changes in reactivity to noradrenaline, 5-hydroxytryptamine or adenosine-5′-triphosphate from those of control DOCA/saline hypertensive rats. Isolated portal veins from rats pretreated with indapamide showed contractile responses to noradrenaline similar to those of control animals although the frequency of spontaneous contractions was reduced in the former group. The results support a vascular site of action for indapamide and suggest a mode of action different from that of hydrochlorothiazide.