Evidence from agonist and antagonist studies to suggest that the beta1-adrenoceptors subserving the positive inotropic and chronotropic responses of the heart do not belong to two separate subgroups

Abstract

The positive inotropic and chronotropic responses of guinea-pig isolated left and right atria to 17 sympathomimetic amines were examined under conditions selected to control the pharmacological environment. Each agonist was compared with (--)-isoprenaline as the reference by constructing dose-response curves. Equiactive molar concentration ratios relative to (--)-isoprenaline were calculated at the EC50 for rate and tension responses. Statistical analysis revealed that (--)-noradrenaline and (+/-)-alpha-methylnoradrenaline were tension selective whereas (+/-)-alpha-ethylisoprenaline and N-methyldopamine were rate selective relative to (--)-isoprenaline. However, no structural trends emerged. The rank order of potency varied slightly between rate and tension, but an analysis of the regression and correlation coefficients indicated respectively that the equiactive molar concentration ratios and the rank orders could be considered identical on rate and tension. Antagonism of the (--)-isoprenaline-induced rate and tension responses by acebutolol, atenolol, practolol and propranolol was assessed from the pA2 values which were almost identical for both parameters with each antagnosti. It is concluded that the beta1-adrenoceptors mediating the positive inotropic and chronotropic responses do not warrant subdivision into two separate groups.