THE BETA-ADRENOCEPTOR ANTAGONIST, NIPRADILOL PRESERVES THE ENDOTHELIAL NITRIC-OXIDE RESPONSE IN ATHEROSCLEROTIC VESSELS OF RABBIT

We evaluated the effects of nipradilol, a beta-adrenoreceptor antagoni st which contains a nitroxy residue, for vascular response in atherosc lerosis of rabbits. Four groups of rabbits received different diets (s tandard diet; standard diet plus 10mg/kg/day nipradilol; atherogenic d iet [standard diet plus 1% cholesterol]; atherogenic diet plus vascula r 10mg/kg/day nipradilol) for 9 weeks. Plasma lipids, blood pressure, function, nitric oxide (NO), activity of NO synthase, cGMP, and histol ogical atherosclerotic changes were evaluated. Neither the atherogenic diet nor nipradilol treatment affected significantly the animals' bod y weight, blood pressure, or heart rate. The atherogenic diet increase d total cholesterol and triglycerides, which were not altered by nipra dilol. The atherogenic diet diminished the acetylcholine-induced NO me diated relaxation. Nipradilol treatment restored this relaxation. Anal yses using a NO-sensitive selective electrode showed that nipradilol r eleased NO in the presence of cells and that NO release was greater in atherosclerotic aorta with than without nipradilol treatment. Nipradi lol treatment increased the basal NO release as evaluated by the aorti c tissue cyclic GMP (cGMP) levels in atherosclerotic vessel, and reduc ed the esterified cholesterol levels in atheroscelerotic vessel. Concl usively, NO released by nipradilol may protect endothelium derived rel axation in atherosclerotic vessels, and may partially inhibit the accu mulation of cholesterol in the atherosclerotic lesions.