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

The effects of indapamide on contractile responses in various isolated artery rings and on spontaneous mechanical activity in portal vein se gments 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. Indapam ide (10(-10)-3 x 10(-4) M) produced a concentration-dependent inhibiti on of the contractile responses induced by high K+ (80 mM), 5-hydroxyt ryptamine (10(-5) M), and noradrenaline (10(-6) or 10(-4) M) in all th e arteries studied. The inhibitory effect was greater in mesenteric (f ifth 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 contractio ns, respectively. Indapamide inhibited in a concentration-dependent ma nner the contractile responses elicited by the addition of Ca2+ (1-5 m M) to Ca2+-free high K+ solution as well as the spontaneous mechanical activity of rat portal vein. Indapamide also reduced the Ca-45(2+) up take 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 depolariza tion- and noradrenaline-induced Ca2+ influx while it did not modify pa ssive Ca2+ entry. Peripheral resistance vessels were demonstrated to b e the arteries most sensitive to indapamide vascular effects.