Effects of indapamide on contractile responses and 45Ca2+ 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. 45Ca2+ 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 Ca(2+)-free high K+ solution as well as the spontaneous mechanical activity of rat portal vein. Indapamide also reduced the 45Ca2+ 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.