Differences between alpha-adrenergic and beta-adrenergic inotropic effects in rat heart papillary muscles.

alpha-And beta-adrenergic inotropic effects have been shown to be qualitatively different. In order to further characterize these difference we compared the mechanical response to alpha- and beta-adrenoceptor stimulation, respectively, in electrically driven left ventricular papillary muscles from rat heart. 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 (first derivate=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 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 considerable increase in T'min (145%) ("Beta-type" effect). Maximal alpha adrenoceptor stimulation increased all qualities by about the same degree (23-24% ("a-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 dose. 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 "a-type" effect although T"min increased significantly more in the absence than in the presence of propranolol and T"min/T'max showed a small increase which developed slowly. Thus Beta-adrenoceptor stimulation 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 calcium influx, the Beta-effect probably is the final result of several subcellular effects of cyclic AMP.