Effect of atenolol and pindolol on the phorbol ester‐induced coronary vasoconstriction in the isolated perfused heart of the rat

1 The effects of atenolol (β 1 ‐adrenoceptor antagonist without partial agonistic activity) and pindolol (β 1 and β 2 ‐antagonist with partial agonistic activity) were studied on basal coronary vascular tone and on the phorbol ester‐induced coronary vasoconstriction in the rat perfused heart. 2 The addition of the phorbol ester 12‐0‐tetradecanoyl‐phorbol‐13‐acetate (TPA; 1.8 × 10 −8 ‐1.6 × 10 −7 m ) into the perfusion fluid during perfusion of rat heart at constant flow caused a dose‐dependent, sustained increase in perfusion pressure. The vasoconstrictor response in hearts of reserpine‐treated rats to infusion of TPA was similar to that of non‐reserpine treated hearts. 3 Infusion of a calcium channel agonist Bay K 8644 at a concentration of 4 × 10 −7 m enhanced, whereas isoprenaline (1 × 10 −5 m ), dibuturyl‐cyclic AMP (1.6 × 10 −4 m ) and forskolin (1 × 10 −6 m ), which elevate intracellular concentrations of cyclic AMP, all inhibited the coronary vasoconstriction induced by TPA. 4 Pindolol, in doses which produced comparable inhibition of isoprenaline‐induced tachycardia, dose‐dependently attenuated the phorbol ester‐induced increase in perfusion pressure, whereas atenolol had no effect. The inhibitory action of pindolol (2 × 10 −5 m ) on TPA‐induced vasoconstriction was blocked by addition of 2.2 × 10 −5 propranolol into the perfusion fluid. When infused alone, atenolol (2 × 10 −4 m ) significantly increased coronary vascular tone, but pindolol had no effect. 5 The present results indicate that pindolol has coronary vasodilator properties due to stimulation of vascular β‐adrenoceptors. If stenosis dilatation of coronary artery spasm is an important component of the anti‐anginal effect of β‐blocking drugs, the possession of partial agonistic property by a β‐blocking drug may be of importance in maintaining coronary flow.