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

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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.