Human myocardial ?-adrenoceptors: demonstration of both ?-adrenoceptors: mediating contractile responses to ?-agonists on the isolated right atrium

Abstract

On the isolated electrically driven muscle strip of human right atrial appendages the β-adrenoceptor subtypes mediating the positive inotropic effects of isoprenaline, dobutamine and procaterol were characterized using the β₁-selective antagonist bisoprolol and the β₂-selective antagonist ICI 118,551. The three agonists induced concentration-dependent increases in force of contraction with an order of potency: procaterol (pD₂-value: 8.03) > isoprenaline (pD₂-value: 7.73) > dobutamine (pD₂-value: 5.44). In saturating concentrations all three agonists produced the same maximum of developed tension. ICI 118,551 (10⁻⁹–10⁻⁷ mol/l) and bisoprolol (10⁻⁹–10⁻⁷ mol/l) were nearly equipotent in antagonizing the positive inotropic effects of isoprenaline and dobutamine. However, the slopes of the Schild-plots for both antagonists against both agonists were significantly less than 1.0 indicating interaction with β₁- and β₂-adrenoceptors. On the other hand, ICI 118,551 (10⁻¹⁰–10⁻⁸ mol/l) was approximately 100 times more potent than bisoprolol (10⁻⁸–10⁻⁶ mol/l) in antagonizing the positive inotropic effect of the highly selective β₂-adrenoceptors procaterol. In addition, the slopes of the Schild-plots for antagonism of ICI 118,551 and bisoprolol against procaterol were not significantly different from unity indicating interaction with a homogeneous class of β-adrenoceptors. The pA₂-value for ICI 118,551 was 9.49, for bisoprolol it amounted to 6.99. These results indicate that on the isolated electrically driven human right atrium isoprenaline and dobutamine produce increases in contractile force via stimulation of β₂-adrenoceptors, while the highly selective β₂-adrenoceptors procaterol induces its positive inotropic effect predominantly through stimulation of β₂-adrenoceptors. It is concluded, therefore, that in human right atrium both β₁- and β₂-adrenoceptors functionally contribute to the cardiac responses of β-agonists.