Postnatal development of β-adrenergic response in ventricular muscle of the rat heart

Abstract

In adult mammalian, heart responses to beta- and alpha-adrenergic stimulation are different: the beta-type effect exhibits a larger increase of relaxation than of contraction, while the alpha-stimulation has no selective influence on relaxation. The present results show that the effect of isoprenaline (ISO) on the neonatal rat heart during the 1st postnatal week is not a typical beta-effect in that the relaxant influence of beta-stimulation is lacking. During the 2nd and 3rd postnatal weeks the typical beta-response, with improved relaxation, gradually appears. The absence of the typical beta-effect is not caused by the lack of beta-receptors or cAMP-dependent phosphorylation reactions because in other respects, the positive inotropic effect of ISO is well developed at the moment of birth. In addition to these qualitative changes, also prominent quantitative changes occurred in the ISO response. The dose-response curves were shifted to the right with advancing age, suggesting reduced beta-agonist potency of the maturing tissue. The developed tension (Tmax) abruptly increased between the 12th and 17th postnatal days and then steeply declined during the next 2 weeks. Changes in Tmax correlated fairly well with the general ability of the tissue to generate extra force, as expressed by rest-dependent potentiation of twitch. However, during the 2nd postnatal week cardiac tissue seemed to be subsensitive to ISO, since all contractile parameters except T''max were depressed. The results suggest that the postnatal changes in beta-response are primarily determined by alternations in the electromechanical coupling process of the developing tissue, and less by the proper adrenergic mechanisms.