title: Effects of indapamide on contractile responses and 45Ca2+ movements in various isolated blood vessels.
abstract: 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.
authors.affiliation: Department of Pharmacology, School of Medicine, Universidad Complutense, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Del Rio
authors.forename: T
authors.initials: T
authors.lastname: Chulia
authors.forename: P
authors.initials: P
authors.lastname: Gonzalez
authors.forename: T
authors.initials: T
authors.lastname: Tejerina
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects; D001488:Basilar Artery / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D004594:Electrophysiology; D005260:Female; D005263:Femoral Artery / Q000187:drug effects; D066298:In Vitro Techniques; D007190:Indapamide / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D011169:Portal Vein / Q000187:drug effects / Q000502:physiology; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D012701:Serotonin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D012701:Serotonin; D011189:Potassium Chloride; D007190:Indapamide; D002118:Calcium; D009638:Norepinephrine