The beta adrenoreceptor antagonist, nipradilol, preserves the endothelial nitric oxide response in atherosclerotic vessels of rabbit.
We evaluated the effects of nipradilol, a beta-adrenoreceptor antagonist which contains a nitroxy residue, for vascular response in atherosclerosis of rabbits. Four groups of rabbits received different diets (standard diet; standard diet plus 10 mg/kg/day nipradilol; atherogenic diet [standard diet plus 1% cholesterol]; atherogenic diet plus 10 mg/kg/day nipradilol) for 9 weeks. Plasma lipids, blood pressure, vascular function, nitric oxide (NO), activity of NO synthase, cGMP, and histological atherosclerotic changes were evaluated. Neither the atherogenic diet nor nipradilol treatment affected significantly the animals' body weight, blood pressure, or heart rate. The atherogenic diet increased total cholesterol and triglycerides, which were not altered by nipradilol. The atherogenic diet diminished the acetylcholine-induced NO mediated relaxation. Nipradilol treatment restored this relaxation. Analyses using a NO-sensitive selective electrode showed that nipradilol released NO in the presence of cells and that NO release was greater in atherosclerotic aorta with than without nipradilol treatment. Nipradilol treatment increased the basal NO release as evaluated by the aortic tissue cyclic GMP (cGMP) levels in atherosclerotic vessel, and reduced the esterified cholesterol levels in atherosclerotic vessel. Conclusively, NO released by nipradilol may protect endothelium derived relaxation in atherosclerotic vessels, and may partially inhibit the accumulation of cholesterol in the atherosclerotic lesions.
Hayashi
T
T
Department of Geriatrics, Nagoya University School of Medicine, Japan.
Yamada
K
K
Esaki
T
T
Muto
E
E
Iguchi
A
A
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000502:physiology; D007150:Immunohistochemistry; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology*; D011817:Rabbits
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D009569:Nitric Oxide; D002784:Cholesterol; D019001:Nitric Oxide Synthase; C036089:nipradilol; D006152:Cyclic GMP