A simple method to determine the ratio of cardiac to vascular beta-receptor blockade in the rat in vivo

Abstract

We have devised a simple method to determine the ratios of cardiac to vascular beta-receptor blockage (C:V ratios) in normotensive rats anesthetized with pentobarbital, and applied it to six beta-adrenergic blocking drugs (beta-blockers). Mean blood pressure (BP) and heart rate (HR) were recorded. Isoproterenol (3 ng-100 microgram/kg, i.v.) was cumulatively injected before and after the intravenous administration of beta-blockers at two dose-levels. Thus shifts of the dose-response curves in BP and HR were observed. "In vivo pA2" values were calculated in molar doses per kg by Schild plots. The C:V ratio was calculated as antilogarithm of the difference of the mean in vivo pA2 value in HR from that in BP. Those of atenolol, bometolol, bunitrolol, pindolol, propranolol, and sotalol were 9.77, 8.13, 2.95, 1.38, 1.20, and 0.71, respectively.