A comparison of the actions of ICI66082 and propranolol on cardiac and peripheral beta-adrenoceptors.

The relative blocking potencies of ICI66082 and propranolol with respect to heart rate contractility, diastolic blood pressure and peripheral vascular conductance were compared in anaesthetized dogs. Peripheral blood flow was measured with an electromagnetic flow-probe around the descending aorta with retrograde cannulation of the inferior mesenteric artery for intra-arterial injections of isoprenaline. Cardiac and peripheral vascular effects of ICI66082 and propranolol were compared in terms of the shifts in the dose--response curves after i.v. and intra-arterial injections of isoprenaline. Propranolol was twice as potent as an equimolar dose of ICI66082 on cardiac beta-adrenoceptors. It was 70--130 times more potent in its action on the peripheral vascular receptors. Propranolol itself was 3 times more potent in blocking peripheral vascular receptors than cardiac beta-receptors. ICI66082 was 17--21 times more active in blocking the myocardial beta-adrenoceptors than those in the peripheral vessels. Electrophysiological studies showed that ICI66082 is devoid of membrane-depressant properties in concentrations up to 100 mg/l.