title: Effects of indapamide on vascular reactivity in hypercholesterolemic rabbits.
abstract: We tested the effects of indapamide (IND), an antihypertensive drug, on the contractile responsiveness of femoral and mesenteric arteries isolated from rabbits fed with a 1% cholesterol diet for 16 weeks. IND (0.1, 0.3, 1 mg/kg/day) was given to the experimental groups of rabbits, whereas control groups received either a standard or a cholesterol-enriched diet. Contractions caused by submaximal doses of norepinephrine (NE) or high-K were significantly decreased in the femoral artery of untreated hypercholesterolemic rabbits. The responses to NE(10(-6) M) or to KCI (80 mM) expressed as a percentage of the control group (standard diet) contractions were 77.0 +/- 3.3% and 55.0 +/- 4.2%, respectively. Vascular reactivity was preserved in the rabbits fed the atherogenic diet supplemented with IND in a concentration-dependent manner. In addition, in the experimental groups dose-response curves to NE (10(-8) to 10(-4) M) and to KCI (20-120 mM) were shifted upward and to the left with respect to the control hypercholesterolemic group. In the mesenteric artery (fifth branch) NE- and K-induced contractions were not significantly altered by hypercholesterolemia. We conclude that IND treatment may prevent femoral arteries from a loss of reactivity probably by reducing the severity of atherosclerosis.
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: T
authors.initials: T
authors.lastname: Tejerina
mesh_terms: D000818:Animals; D002791:Cholesterol, Dietary; D004305:Dose-Response Relationship, Drug; D005263:Femoral Artery / Q000187:drug effects; D006937:Hypercholesterolemia / Q000503:physiopathology*; 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; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D002791:Cholesterol, Dietary; D011189:Potassium Chloride; D007190:Indapamide; D009638:Norepinephrine