The role of sympathetic activity in atherogenesis: effects of beta-blockade.
Clinical and experimental evidence points to potential antiatherosclerotic effects of certain beta-adrenoreceptor antagonists. Long-term treatment with metoprolol resulted in significant reductions of total and cardiovascular mortality or morbidity due to decreased incidence of coronary and cerebrovascular complications both in a primary prevention trial in hypertensive patients and in a secondary prevention trial in patients surviving myocardial infarction. The observations suggest that a retardation of atherosclerosis development might have contributed to the reduced incidence of cardiovascular complications. An antiatherosclerotic effect of beta-blockers has been directly demonstrated in animal studies. In cholesterol-fed rabbits, metoprolol significantly reduced the development of atherosclerotic plaques in the aortic intima in the absence of any changes in blood lipids. Similar findings were reported for propranolol, which prevented psychosocial stress-induced atherosclerosis of the coronary artery in monkeys. Furthermore, beta-blockers have been shown to prevent stress-induced endothelial injury and platelet accumulation to intima at atherosclerotic predilection sites in animal models. These antiatherogenic effects may be due to biochemical and hemodynamic factors. Two biochemical effects of beta-blockade may lead to reduced cholesterol accumulation in arterial intima at unchanged serum cholesterol levels. One is a beta-blocker-induced increase of prostacyclin biosynthesis, and the other a metabolic change of low-density lipoprotein, reducing its potential for deposition in the arterial wall. The antiatherogenic effect of these factors may be reinforced by beta-blocker-induced hemodynamic changes leading to reductions of arterial flow aberrations and pressure-related wall stress.
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*
D000319:Adrenergic beta-Antagonists