Vasorelaxant actions of 5-OH-indapamide, a major metabolite of indapamide: comparison with indapamide, hydrochlorothiazide and cicletanine.

5-OH-Indapamide is a principal metabolite of indapamide, and possesses similar antihypertensive and diuretic properties. This study investigated the mechanisms of the acute vasodilator actions of 5-OH-indapamide, indapamide, hydrochlorothiazide and cicletanine and their interaction with ion channels in isolated guinea pig mesenteric arteries. Hydrochlorothiazide, cicletanine and 5-OH-indapamide relaxed noradrenaline-constricted vessels significantly more than K(+)-constricted vessels (P < 0.001) and the relaxations were reduced in the presence of charybdotoxin (P < 0.001). 5-OH-Indapamide-induced relaxation was reduced (by 42% at 30 microM) by glibenclamide (P < 0.001). Hydrochlorothiazide, cicletanine and 5-OH-indapamide (all at 10 microM) were weak Ca2+ antagonists shifting the Ca2+ dose-response curves half a log unit to the right (P < 0.01). Indapamide was a more potent inhibitor, a 10 microM concentration shifting the Ca2+ dose-response curve three log units to the right and reducing maximal-induced Ca2+ contraction by 72% (P < 0.001). Hydrochlorothiazide, cicletanine and 5-OH-indapamide-induced relaxations appear to be partly mediated via Ca(2+)-activated K+ channels; 5-OH-Indapamide-induced relaxation is also partly mediated via ATP-sensitive K+ channels. Indapamide is a potent Ca2+ antagonist.