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

Br J Pharmacol. 1988 Jun;94(2):573-83. doi: 10.1111/j.1476-5381.1988.tb11563.x.

Abstract

1. The effects of atenolol (beta 1-adrenoceptor antagonist without partial agonistic activity) and pindolol (beta 1- and beta 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 X 10(-8)-1.6 X 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 X 10(-7) M enhanced, whereas isoprenaline (1 X 10(-5) M), dibuturyl-cyclic AMP (1.6 X 10(-4) M) and forskolin (1 X 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 X 10(-5) M) on TPA-induced vasoconstriction was blocked by addition of 2.2 X 10(-5) M propranolol into the perfusion fluid. When infused alone, atenolol (2 X 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 beta-adrenoceptors. If stenosis dilatation of coronary artery spasm is an important component of the anti-anginal effect of beta-blocking drugs, the possession of partial agonistic property by a beta-blocking drug may be of importance in maintaining coronary flow.

MeSH terms

  • Animals
  • Atenolol / pharmacology*
  • Coronary Vessels / drug effects*
  • Heart / drug effects
  • In Vitro Techniques
  • Male
  • Perfusion
  • Phorbol Esters / pharmacology*
  • Pindolol / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Receptors, Adrenergic, beta / drug effects
  • Receptors, Adrenergic, beta / physiology
  • Vasoconstriction / drug effects*

Substances

  • Phorbol Esters
  • Receptors, Adrenergic, beta
  • Atenolol
  • Pindolol