Ja. Calder et al., VASORELAXANT ACTIONS OF 5-OH-INDAPAMIDE, A MAJOR METABOLITE OF INDAPAMIDE - COMPARISON WITH INDAPAMIDE, HYDROCHLOROTHIAZIDE AND CICLETANINE, European journal of pharmacology, 256(2), 1994, pp. 185-191
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.