Adrenergic beta receptor blockade: hemodynamic importance of intrinsic sympathomimetic activity at rest.

Abstract

Dose-response curves for heart rate, cardiac output, arterial blood pressure, and pulmonary artery pressure were obtained in 37 patients with ischemic heart disease after intravenous administration of six increasing doses of propranolol, atenolol, practolol, pindolol, CPEP (1 -[2-cyanophenoxy]-3β-[3-phenylureido]-ethylamino-2-propanol), and BMMP (1-t-butylamino-3-[2-N-methylcarbamoyl-methoxyphenoxy]propan-2-ol-hydrochloride). The doses were equipotent, as indicated by reduction in exercise-induced tachycardia. The dose-response curves for cardiac output and heart rate can be divided into three groups according to the degree of intrinsic sympathomimetic activity. One group without intrinsic sympathomimetic activity included propranolol and atenolol, which reduced cardiac output (about 26% to 28%) and heart rate (about 15% to 17%). A second group with moderate intrinsic sympathomimetic activity, represented by practolol and BMMP, induced less reduction in cardiac output (about 12% to 17%) and heart rate (about 7% to 10%). A third group with pronounced intrinsic sympathomimetic activity, represented by pindolol and CPEP, did not reduce cardiac output and heart rate. Mean systemic blood pressure was essentially unchanged even after the largest dose of any of the drugs. Mean pulmonary artery pressure rose after atenolol, propranolol, and BMMP but not after pindolol, CPEP, and practolol. Atenolol, BMMP, and practolol are beta-1–selective drugs, it is concluded that the acute hemodynamic response to adrenergic beta receptor blocking drugs at rest is determined primarily by the degree of intrinsic sympathomimetic activity, whereas beta-1 selectivity did not modify the central hemodynamic responses to beta adrenoceptor blockade. Clinical Pharmacology and Therapeutics (1981) 29, 711–718; doi:10.1038/clpt.1981.100