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 investig ated the mechanisms of the acute vasodilator actions of 5-OH-indapamid e, indapamide, hydrochlorothiazide and cicletanine and their interacti on with ion channels in isolated guinea pig mesenteric arteries. Hydro chlorothiazide, 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 charybdot oxin (P < 0.001). 5-OH-Indapamide-induced relaxation was reduced (by 4 2% at 30 mu M) by glibenclamide (P < 0.001). Hydrochlorothiazide, cicl etanine and 5-OH-indapamide (all at 10 mu M) were weak Ca2+ antagonist s shifting the Ca2+ dose-response curves half a log unit to the right (P < 0.01). Indapamide was a more potent inhibitor, a 10 mu M concentr ation shifting the Ca2+ dose-response curve three log units to the rig ht and reducing maximal-induced Ca2+ contraction by 72% (P < 0.001). H ydrochlorothiazide, cicletanine and 5-OH-indapamide-induced relaxation s appear to be partly mediated via Ca2+-activated K+ channels; 5-OH-In dapamide-induced relaxation is also partly mediated via ATP-sensitive K+ channels. Indapamide is a potent Ca2+ antagonist.