Both alpha 1- and beta-adrenoceptor stimulation determine the time course of the inotropic effect of noradrenaline in rabbit heart

Pharmacol Toxicol. 1990 Aug;67(2):172-7. doi: 10.1111/j.1600-0773.1990.tb00806.x.

Abstract

It has been a matter of controversy whether alpha 1-adrenoceptor stimulation contributes to the final inotropic and lusitropic responses in mammalian myocardium to noradrenaline during concomitant and unopposed beta-adrenoceptor stimulation. In the present paper we report studies that compare time courses of the inotropic and lusitropic responses to separate and combined alpha 1- and beta-adrenoceptor stimulation, respectively, in electrically driven rabbit papillary muscles by a submaximal concentration of noradrenaline. Separate alpha 1- or beta-adrenoceptor stimulation (presence of appropriate receptor blocker) showed the characteristic slow and fast development, respectively, of the inotropic responses. Qualitatively, the respective characteristic changes were also observed: alpha 1-adrenoceptor stimulation caused a negative lusitropic effect giving a prolongation of the time to peak tension (TPT), while beta-adrenoceptor stimulation caused a pronounced positive lusitropic effect giving a shortening of TPT. The time course of the inotropic response to combined adrenoceptor stimulation had characteristics that deviated from the respective time courses to separate alpha 1- or beta-adrenoceptor stimulation thus indicating a contribution from both adrenoceptor populations to the final inotropic response. Combined alpha 1- and beta-adrenoceptor stimulation gave a pronounced positive lusitropic response as might be expected due to the obviously dominating role of the beta-adrenergic component. However, the maximal lusitropic effect and the shortening of TPT were both slightly less during combined adrenoceptor stimulation compared to separate beta-stimulation thus indicating an influence of the alpha 1-adrenoceptor mediated negative lusitropic effect. Quantitatively, the separate alpha 1- and the separate beta-adrenoceptor mediated inotropic effects were not additive. In accordance with other recent studies, this indicated an inhibitory interaction between the two adrenergic receptor populations in myocardium.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Myocardial Contraction / drug effects*
  • Norepinephrine / pharmacology*
  • Papillary Muscles / drug effects
  • Prazosin / pharmacology
  • Propranolol / pharmacology
  • Rabbits
  • Receptors, Adrenergic, alpha / drug effects*
  • Receptors, Adrenergic, beta / drug effects*
  • Time Factors

Substances

  • Receptors, Adrenergic, alpha
  • Receptors, Adrenergic, beta
  • Propranolol
  • Norepinephrine
  • Prazosin