A comparison of the effects of adrenaline and noradrenaline on human heart: the role of 1- and 2-adrenoceptors in the stimulation of adenylate cyclase and contractile force

Abstract

The stimulant effects of adrenaline and noradrenaline on contractile force and adenylate cyclase, mediated through β₁- and β₂-adrenoceptors, are analysed in isolated atrial and ventricular myocardium of man. The tissues were obtained from patients without advanced heart failure undergoing heart surgery. Usually, both adrenaline and noradrenaline stimulated adenylate cyclase predominantly through ventricular and atrial β₂-adrenoceptors. Because the relative density of β₂-adrenoceptors is usually smaller than that of β₁-adrenoceptors, stimulation of one β₂-adrenoceptor leads to the production of up to 10 times more cyclic AMP molecules than does stimulation of one β₁-adrenoceptor. Adrenaline and noradrenaline maximally enhance contractile force through both atrial and ventricular β₁-adrenoceptors. Adrenaline can also maximally enhance contractile force through atrial β₂-adrenoceptors. In the ventricle, adrenaline increases force via β₂-adrenoceptors by up to 60% of its maximal β₁ response. Noradrenaline can increase atrial and ventricular contractile force through β₂-adrenoceptors but only at high concentrations. Unexpectedly, in atria from patients treated with the β₁-selective antagonist atenolol, contractile responses to adrenaline are markedly and selectively augmented through activation of β₂-adrenoceptors. In atria from atenolol-treated patients equi-inotropic concentrations of adrenaline and noradrenaline acting through β₂- and β₁-adrenoceptors, respectively, cause similar increases of cyclic AMP and of cyclic AMP-dependent protein kinase activity.