Effects of indapamide on endothelium-dependent relaxations in isolated canine femoral arteries.
Indapamide is an effective antihypertensive agent in humans and in experimental hypertensive animals. The aim of the present study was to investigate whether indapamide affects endothelium-dependent and independent relaxations in canine femoral arteries. Rings (with or without endothelium) were contracted with prostaglandin F2 alpha (2 X 10(-6) mol/liter) before the addition, in a cumulative fashion, of relaxing agents. Indapamide (10(-7) to 10(-4) mol/liter) had no direct effect on unstimulated or prostaglandin-stimulated preparations; it did not alter relaxations of preparations with endothelium induced by acetylcholine, bradykinin, adenosine diphosphate or the calcium ionophore A23187. Similarly, it did not affect relaxations induced by sodium nitroprusside, prostacyclin or forskolin in preparations with or without endothelium. Indomethacin shifted the concentration-response curve to bradykinin to the right and did not alter that to the other relaxing drugs. The reduced relaxation to bradykinin was reversed in a concentration-dependent manner by indapamide (10(-7) to 10(-5) mol/liter). In the presence of indomethacin, indapamide shifted the concentration response curve to prostacyclin (in rings with endothelium) and to forskolin (in rings with and without endothelium) to the left. Thus, indapamide does not directly affect endothelium-dependent and independent relaxations. However, when prostanoid production is impaired, indapamide facilitates the release of endothelium-derived relaxing factor(s), and to a lesser extent, the direct action on vascular smooth muscle of prostanoids (prostacyclin) released from the endothelium.
Schini
V B
VB
Center for Experimental Therapeutics, Baylor College of Medicine, Houston, Texas 77030.
Dewey
J
J
Vanhoutte
P M
PM
D000109:Acetylcholine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology; D004232:Diuretics / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects*; D011464:Epoprostenol / Q000494:pharmacology; D005260:Female; D005263:Femoral Artery / Q000187:drug effects*; D007190:Indapamide / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000493:pharmacokinetics; D014664:Vasodilation / Q000187:drug effects
D004232:Diuretics; D005576:Colforsin; D009569:Nitric Oxide; D000001:Calcimycin; D000244:Adenosine Diphosphate; D015237:Dinoprost; D011464:Epoprostenol; D007190:Indapamide; D000109:Acetylcholine; D001920:Bradykinin; D007213:Indomethacin