Effects of the beta2-adrenoceptor agonists fenoterol and salbutamol on force of contraction in isolated human ventricular myocardium

Abstract

The effects of fenoterol and salbutamol on isometric force of contraction were studied in isolated, electrically driven human papillary muscle preparations. Fenoterol increased force of contraction at concentrations of 1 mumol l-1 and higher. The maximally effective concentration of fenoterol (100 mumol l-1) increased force of contraction by about 130%. The positive inotropic effect of fenoterol was not influenced by 0.1 mumol l-1 prazosin. The beta 1-selective antagonist atenolol (2 mumol l-1) and the beta 2-selective antagonist ICI 118551 (1 mumol l-1) shifted the concentration-response curve of fenoterol to the right, indicating that beta 1- and beta 2-adrenoceptors may contribute to the positive inotropic effect of fenoterol. In contrast to fenoterol, salbutamol increased force of contraction only by about 11% at 100 mumol l-1. The results indicate that: (1) fenoterol exerts a direct positive inotropic effect in the human heart which may support the beneficial effects of the reduction of systemic vascular resistance in patients with congestive heart failure; (2) this positive inotropic effect of fenoterol is mediated by beta 1- and beta 2-adrenoceptors; (3) the clinically observed improvement of cardiac performance in the case of salbutamol is presumably not due to any direct positive inotropic effect.