Both alpha 1- and beta-adrenoceptor stimulation determine the time course of the inotropic effect of noradrenaline in rabbit heart.
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.
Skomedal
T
T
Department of Pharmacology, University of Oslo, Norway.
Aass
H
H
Osnes
J B
JB
D000818:Animals; D009200:Myocardial Contraction / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology*; D010210:Papillary Muscles / Q000187:drug effects; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013997:Time Factors
D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D011433:Propranolol; D009638:Norepinephrine; D011224:Prazosin