Differences between α‐Adrenergic and β‐Adrenergic Inotropic Effects in Rat Heart Papillary Muscles

Abstract

a-And p-adrenergic inotropic effects have been shown to be qualitatively different. In order to further characterize these differences we compared the mechanical responses to a-and P-adrenoceptor stimulation, respectively, in electrically driven left ventricular papillary muscles from rat heart. The muscles were stimulated by either isoprenaline (p-adrenoceptor stimulation), phenylephrine in the presence of propranolol (a-adrenoceptor stimulation) or phenylephrine alone (combined aand p-adrenoceptor stimulation). 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. These recordings disclosed qualitative differences between the a-and p-inotropic response both in dose-response and time course experiments. Maximal p-adrenoceptor stimulation caused a small increase in T,,, (I8 %), intermediate increases in T',,, (45%) and T',,, (68%) and a considerable increase in T",,, (145%) ("/I-type" effect). Maximal aadrenoceptor stimulation increased all qualities by about the same degree (23-24%) ("a-type" effect). While padrenoceptor stimulation gave a dose-dependent and pronounced increase in the ratio T",,n/T',,, (relaxationonset index), a-adrenoceptor stimulation decreased it to subcontrol values and phenylephrine alone gave a small dose-dependent increase at higher doses. The time course of the a-adrenoceptor stimulation was characterized by a transient decrease in all qualities followed by an increase which reached maximum at 4-5 min. p-Adrenoceptor stimulation gave a monophasic response which reached maximum after 1-2 min. Phenylephrine alone gave mainly an "a-type" effect although T",,. increased significantly more in the absence than in the presence of propranolol and T,,n/T',ax showed a small increase which developed slowly. Thus p-adrenoceptor stimulation activated relaxation compared to contraction by a higher degree than did a-adrenoceptor stimulation. This probably reflects different mechanisms of action. While the a-effect may rely primarily on an increased calcium influx, the p-effect probably is the final result of several subcellular effects of cyclic AMP. Key-words:Rat hearta-adrenergic effectsp-adrenergic effectscyclic AMPrat. W h e n Ahlquist classified adrenergic receptors in 1948, he designated the stimulating receptors in heart P-adrenergic according t o t h e o r d e r of potency of a number of agonists (Ahlquist 1948). p-Receptors were regarded a s t h e sole adrenoceptors in heart muscle for m a n y years, although Nickerson (1949) had published results indicating an a-adrenergic inotropic effect in frog heart. In 1966,Wenzel & Su, however, claimed t h a t ventricle strips from rat heart contained both aa n d P-adreno-ceptors a s recorded by inotropic effects. Later

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