Adrenoceptors in myocardial regulation: concomitant contribution from both alpha- and beta-adrenoceptor stimulation to the inotropic response.
The studies presented deal with the alpha 1-adrenoceptor mediated inotropic effects of noradrenaline obtained by exclusive ("pure") alpha 1-adrenoceptor stimulation or by concomitant stimulation of alpha 1- and beta-adrenoceptors in myocardium. The pure beta-adrenergic effects of noradrenaline were also quantified. Interactions between the two receptor systems were studied. The pure alpha 1- and beta-adrenergic effects of noradrenaline, respectively, were achieved separately in the presence of high concentrations of appropriate receptor blockers. The experiments were performed on isolated ventricular myocardium from rat, rabbit, and man. The pure alpha 1-adrenergic inotropic effects were about 35-50% of control (basal) and half the pure beta-adrenergic effects both in rat and rabbit myocardium. Ventricular myocardium from man exhibited an alpha 1-adrenergic inotropic effect of the same magnitude (50% of control [basal]) as did rabbit papillary muscle. Determination of the alpha 1-adrenergic inotropic component during concomitant beta-adrenoceptor stimulation was associated with difficulties. Several experimental approaches on rat and rabbit myocardium are presented and discussed. Some types of experimental approaches obviously underestimate the alpha 1-adrenergic component. The methods regarded as reliable revealed an alpha 1-adrenergic inotropic effect of about 20-30% during combined adrenoceptor stimulation by noradrenaline. Concomitant beta-stimulation reduced the alpha 1-adrenergic effect by about 50%, while alpha 1-stimulation attenuated the beta-effect to a lesser degree (about 20-25%). A model is presented on a mutual attenuation of the functional expression of the two receptor systems.(ABSTRACT TRUNCATED AT 250 WORDS)
Osnes
J B
JB
Department of Pharmacology, University of Oslo, Norway.
Aass
H
H
Skomedal
T
T
D000818:Animals; D009200:Myocardial Contraction / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D009638:Norepinephrine