EFFECTS OF INDAPAMIDE ON CONTRACTILE RESPONSES AND CA-45(2+) MOVEMENTS IN VARIOUS ISOLATED BLOOD-VESSELS

The effects of indapamide on contractile responses in various isolated artery rings and on spontaneous mechanical activity in portal vein segments were investigated. Arteries used were: rabbit aorta, mesenteric (fifth branch). femoral and basilar, and sheep coronary arteries. Ca-45(2+) uptake was also analysed in rabbit mesenteric arteries. Indapamide (10(-10)-3 x 10(-4) M) produced a concentration-dependent inhibition of the contractile responses induced by high K+ (80 mM), 5-hydroxytryptamine (10(-5) M), and noradrenaline (10(-6) or 10(-4) M) in all the arteries studied. The inhibitory effect was greater in mesenteric (fifth branch) the IC50 values being 9.2 +/- 3.0 x 10(-6) and 5.5 +/- 4.0 x 10(-8) M for depression of high K+- and agonist-induced contractions, respectively. Indapamide inhibited in a concentration-dependent manner the contractile responses elicited by the addition of Ca2+ (1-5 mM) to Ca2+-free high K+ solution as well as the spontaneous mechanical activity of rat portal vein. Indapamide also reduced the Ca-45(2+) uptake in rabbit mesenteric arteries stimulated by noradrenaline (10(-4) M) or by high K+ (80 mM) without affecting the Ca2+ influx in resting tissues. Our results indicate that indapamide blocked both depolarization- and noradrenaline-induced Ca2+ influx while it did not modify passive Ca2+ entry. Peripheral resistance vessels were demonstrated to be the arteries most sensitive to indapamide vascular effects.