Haemodynamic consequences of intrinsic sympathomimetic activity and cardioselectivity in beta-blocker therapy for hypertension.

Abstract

The relevance of intrinsic sympathomimetic activity (ISA) and cardioselectivity for the acute and long-term haemodynamic effects of beta-blocker therapy for hypertension was assessed from reports in the literature. The beta-blockers included in this survey are pindolol, practolol, alprenolol, oxprenolol, acebutolol, penbutolol, metoprolol, atenolol, propranolol and timolol. Forty-four acute and 41 long-term studies in 430 and 482 subjects respectively, were analysed. In acute studies arterial pressure is barely lowered, whereas in spite of the many pharmacological and physicochemical differences beta-blockers appear to have a hypotensive effect of approximately equal magnitude during long-term treatment. In the acute studies, the falls in heart rate, stroke volume, cardiac output and subsequently increased total peripheral resistance are inversely proportional to the pharmacologically defined quantity of ISA of the beta-blockers. The response of vascular resistance to cardiodepression is similar for non-selective and beta 1-selective agents. During long-term therapy, the inverse correlation between cardiac output and vascular resistance is shifted to a lower level of vascular resistance. This reduction of vascular resistance at any level of cardiac output that underlies the hypotensive action of beta-blockers is associated with an increase in stroke volume. Thus, the absolute value of vascular resistance during beta-blocker therapy is determined by the degree of ISA, irrespective of the quality of cardioselectivity. Consequently, beta-blockers with sufficient ISA to prevent disturbance of tissue perfusion at rest reduce the characteristically elevated vascular resistance in longstanding arterial hypertension in contrast with beta-blockers lacking this property. This can have implications for the long-term prognosis of this condition.