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

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Abstract
.alpha.-A and .beta.-adrenergic inotropic effects are qualitatively different. The mechanical responses to .alpha.- and .beta.-adrenoceptor stimulation in electrically driven left ventricular papillary muscles from rat heart were compared. The muscles were stimulated by either isoprenaline (.beta.-adrenoceptor stimulation), phenylephrine in the presence of propranolol(.alpha.-adrenoceptor stimulation) or phenylephrine alone (combined .alpha.- and .beta.-adrenoceptor stimulation). Isometric tension (T), rate of rise and decline of tension (1st derivative = T'') and rate of transition from tension rise to tension decline (negative part of 2nd derivative = T") were recorded. These recordings disclosed qualitative differences between the .alpha.- and .beta.-inotropic response both in dose-response and time course experiments. Maximal .beta.-adrenoceptor stimulation caused a small increase in Tmax (18%), intermediate increases in T''max (45%) and T''min (68%) and a considerable increase in T"min (145%) (.beta.-type effect). Maximal .alpha.-adrenoceptor stimulation increased all qualities by about the same degree (23-24%) (.alpha.-type effect). While .beta.-adrenoceptor stimulation gave a dose-dependent and pronounced increase in the ratio T"min/T''max (relaxation-onset index), .alpha.-adrenoceptor stimulation decreased it to subcontrol values and phenylephrine alone gave a small dose-dependent increase at higher doses. The time course of the .alpha.-adrenoceptor stimulation was characterized by a transient decrease in all qualities followed by an increase which reached maximum at 4-5 min. .beta.-Adrenoceptor stimulation gave a monophasic response which reached maximum after 1-2 min. Phenylephrine alone gave mainly an .alpha.-type effect although T"min increased more in the absence than in the presence of propranolol and T"min/T''max showed a small increase which developed slowly. .beta.-Adrenoceptor stimulation apparently activated relaxation compared to contraction by a higher degree than did .alpha.-adrenoceptor stimulation. This probably reflects different mechanisms of action. While the .alpha.-effect may rely primarily on an increased Ca influx, the .beta.-effect probably is the final result of several subcellular effects of cAMP.