Qualitative differences between the inotropic responses in rat papillary muscles to alpha-adrenoceptor and beta-adrenoceptor stimulation by both noradrenaline and adrenaline.

Abstract

Abstract: Mammalian heart has obviously both α‐ and β‐adrenergic inotropic mechanisms, and stimulation of these two mechanisms by appropriate agonists lead to qualitatively different inotropic responses. This difference can serve to recognize the two adrenergic inotropic effects. In order to explore if the endogenous catecholamines, noradrenaline and adrenaline, could activate both these mechanisms, and if so, to characterize them qualitatively and quantitatively, the mechanical responses in electrically driven rat left ventricular papillary muscles were examined in the absence or presence of appropriate receptor blockade. Isometric tension (T), rate of rise and decline of tension (first derivative = T) and rate of transition from tension rise to tension decline (negative part of second derivative=T) were recorded. α‐Adrenergic and β‐adrenergic inotropic effects were demonstrated both for noradrenaline and adrenaline. Maximal β‐adrenoceptor stimulation (agonist in the presence of an α‐adrenoceptor blocker) caused a small increase in Tmax, intermediate increases in T'max and T'min, and a considerable increase in Tmin (β‐type effect). Maximal α‐adrenoceptor stimulation (agonist in the presence of a β‐adrenoceptor blocker) increased all parts of the contraction‐relaxation cycle by about the same degree (TminTminT'maxTmax α‐type effect). While β‐adrenoceptor stimulation gave a dose dependent and pronounced increase in the ratio Tmin/Tmax (relaxation‐onset index), α‐adrenoceptor stimulation decreased it to subcontrol values. The time course of the response to the α‐adrenoceptor stimulation was characterized by a transient decrease in all qualities followed by an increase which reached maximum at 4–5 min. β‐Adrenoceptor stimulation gave a monophasic inotropic response which developed in the course of 1–2 min. Both agents alone gave a monophasic response with the characteristics of a β‐type effect (i.e. relative maximal increase of TminTminTmaxTmax), and a marked increase in the relaxation‐onset index (Tmin/Tmax). Thus the β‐adrenergic inotropic component was the dominating one when the amines were used alone. The two different response patterns probably reflect a dual mechanism of action of the endogenous catecholamines: the β‐adrenergic component which is dependent upon an increase in cyclic AMP levels and the α‐adrenergic component which is independent on cyclic AMP.