Effects of indapamide on vascular reactivity in hypercholesterolemic rabbits.
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.
Del Rio
M
M
Department of Pharmacology, School of Medicine, Universidad Complutense, Madrid, Spain.
Chulia
T
T
Tejerina
T
T
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*
D002791:Cholesterol, Dietary; D011189:Potassium Chloride; D007190:Indapamide; D009638:Norepinephrine