Carvedilol inhibits aortic lipid deposition in the hypercholesterolemic rat.
The effects of carvedilol, a vasodilating beta-blocker with antioxidant activity, and nifedipine, a calcium channel blocker, were investigated on aortic lipid deposition and the accumulation of monocytes and foam cells at the sites of atherosclerotic lesions in rats subjected to a hypercholesterolemic diet. Fifty rats were randomly assigned to the following experimental groups: (1) regular rat chow (n = 5); (2) regular rat chow supplemented with a high-cholesterol diet (1% cholesterol and 1% cholic acid; n = 15); (3) a high-cholesterol diet plus nifedipine (n = 15), and (4) a high-cholesterol diet plus carvedilol (n = 15). Animals were maintained on these diets for 12 weeks. None of the treatment groups had blood pressures that were outside the normotensive range, and no significant differences in plasma lipid levels were observed among the high-cholesterol diet and drug-treated groups. There was a significantly lower lipid content (p < 0.001) in the thoracic aortas of the nifedipine-treated (211 +/- 23 nmol/mm2) and carvedilol-treated (182 +/- 23 nmol/mm2) groups compared to cholesterol-fed controls (242 +/- 27 nmol/mm2). Furthermore, carvedilol-treated animals showed significantly less (p < 0.001) lipid accumulation than did the nifedipine-treated animals. The number of monocytes and foam cells were decreased in both drug-treated groups compared to animals receiving high-cholesterol diets without drug treatment. The results demonstrate that treatment with carvedilol or nifedipine can significantly inhibit lipid deposition in the aorta and reduce monocyte and foam cell accumulation, and that carvedilol is significantly more effective than nifedipine in inhibiting lipid deposition.
Feuerstein
G Z
GZ
Department of Neurology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406-0939, USA.
Fisher
M
M
Nunnart
J
J
Ruffolo
R R
RR
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology; D001161:Arteriosclerosis / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D002227:Carbazoles / Q000627:therapeutic use*; D000077261:Carvedilol; D006937:Hypercholesterolemia / Q000150:complications / Q000188:drug therapy*; D050356:Lipid Metabolism; D008297:Male; D009543:Nifedipine / Q000627:therapeutic use; D011412:Propanolamines / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000627:therapeutic use*
D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D002227:Carbazoles; D011412:Propanolamines; D014665:Vasodilator Agents; D000077261:Carvedilol; D009543:Nifedipine