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.
机构:
UNIV TEXAS,SW MED SCH,DEPT PHARMACOL,5323 HARRY HINES BLVD,DALLAS,TX 75235UNIV TEXAS,SW MED SCH,DEPT PHARMACOL,5323 HARRY HINES BLVD,DALLAS,TX 75235
GOODMAN, FR
WEISS, GB
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机构:
UNIV TEXAS,SW MED SCH,DEPT PHARMACOL,5323 HARRY HINES BLVD,DALLAS,TX 75235UNIV TEXAS,SW MED SCH,DEPT PHARMACOL,5323 HARRY HINES BLVD,DALLAS,TX 75235
WEISS, GB
ADAMS, HR
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UNIV TEXAS,SW MED SCH,DEPT PHARMACOL,5323 HARRY HINES BLVD,DALLAS,TX 75235UNIV TEXAS,SW MED SCH,DEPT PHARMACOL,5323 HARRY HINES BLVD,DALLAS,TX 75235
ADAMS, HR
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS,
1974,
188
(02):
: 472
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480