MODULATION OF ADRENERGIC-RECEPTORS DURING REGRESSION OF CARDIAC-HYPERTROPHY

Objective: To determine whether alpha(1)- or beta-adrenergic receptors are altered during regression of cardiac hypertrophy produced by anti hypertensive agents. Design and methods: Cardiac hypertrophy was induc ed in rats by aortic banding. After 6 weeks banding the rats were trea ted with an angiotensin converting enzyme (ACE) inhibitor (enalapril), an alpha(1)-adrenergic antagonist (bunazosin) or a beta-adrenergic an tagonist (propranolol) for 6 weeks to induce regression. The numbers o f alpha(1)- and beta-adrenergic receptors, haemodynamics, tissue norad renaline content and tissue ACE activity were measured. Results: Regre ssion of cardiac hypertrophy occurred after treatment of aortic banded rats with a high dose of enalapril, bunazosin or propranolol, and was accompanied by a reduction in systolic blood pressure. The number of alpha(1)- or beta-adrenergic receptors was unchanged by propranolol tr eatment, but the number of alpha(1)-adrenergic receptors was increased in the hearts of rats treated with bunazosin. A low dose of enalapril (3 mg/kg body weight) caused regression of hypertrophy without a conc omitant reduction in blood pressure, and decreased the number of alpha (1)-adrenergic receptors. The dissociation constants for alpha(1)- and beta-adrenergic receptors were not different among the experimental g roups, and the positive derivatives of left ventricular pressure was u naltered in rats treated with a low dose of enalapril but was reduced by the other drugs. Conclusion: Of the three drugs tested, only the lo w dose of enalapril affected adrenergic receptors during regression of cardiac hypertrophy, causing a decrease in alpha(1)-adrenergic recept or number without a reduction in blood pressure. This effect may be ex plained by non-haemodynamic actions of the ACE inhibitor enalapril, pr obably by modulation of peripheral sympathetic activity.