Qualitative differences between beta-adrenergic and alpha-adrenergic inotropic effects in rat heart muscle.
If beta- and alpha-adrenergic inotropic effects are cyclic AMP dependent and cyclic AMP independent, respectively, they may be qualitatively different. The inotropic effects of beta-receptor stimulation (isoprenaline) and alpha-receptor stimulation (phenylephrine combined with propranolol) were characterized in isolated perfused rat hearts, rat atria and rat papillary muscles. The beta-effect reached its maximum before the alpha-effect. The alpha-effect followed a three-phasic time-course indicating both stimulatory and inhibitory components. The aortic pressure wave (perfused heart) indicated a shorter contraction phase after beta-stimulation than after alpha-stimulation. The time to peak tension (atrium, papillary muscle) was relatively shorter after isoprenaline than after alpha-stimulation, which tended to prolong it. The contraction-relaxation cycles (atrium, papillary muscle) were examined by recording the isometric tension (T), its first (T') and second (T'') deri derivatives. alpha and beta-stimulation both increased Tmax, T'max (maximal rate of tension rise), T'min (maximal rate of tension decline) and T''min (maximal rate of transition from rise to decline of tension). Isoprenaline increased T'min (papillary muscle) and T''min (atrium, papillary muscle) relatively more than did alpha-stimulation, i.e. the relaxing processes were activated relatively more by beta-stimulation. The results indicate different mechanisms for the two adrenergic inotropic effects. The relatively larger activation of relaxation by beta-stimulation is assumed to be caused by clic AMP.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D000242:Cyclic AMP / Q000502:physiology; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects; D010477:Perfusion; D010656:Phenylephrine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D010656:Phenylephrine; D011433:Propranolol; D000242:Cyclic AMP; D007545:Isoproterenol