CONTRASTING CELLULAR EFFECTS OF BETA1 AND BETA2 ADRENERGIC RECEPTOR STIMULATION

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The mechanical effects mediated by beta 2-adrenoceptor stimulation were studied in isolated rat ventricular myocytes. Beta 2-adrenoceptor stimulation was induced by using beta 2-selective agonist Zinterol and isoproterenol (ISO) in the presence of beta 1-selective antagonist CGP- 20712A. ICI was used as a selective beta 2-antagonist. Zinterol has an apparent positive inotropic effect which was associated with an increase in Cai transient. In addition, ISO in the presence of selective beta 1- blocker CGP-20712A has very similar effects on contraction and Cai transient. Both the effect of Zint and ISO can be antagonized by beta 2- blocker ICI 118,551, but not by CGP. Furthermore, the comparative data of beta 2 vs. beta 1-adrenoceptor stimulation show that there are some striking differences of cell responses to beta 1 and beta 2-adrenergic stimulation. For a given level of inotropic effect, beta 2 receptor stimulation has less effects on the time course of contraction and Cai transient on the myofilament sensitivity to Ca i, and is less arrhythmogenic than beta 1 receptor stimulation. These results demonstrate for the first time that in rat myocardium beta 2-adrenoceptors functionally coexist with beta 1-adrenoceptors and suggest that the cAMP stimulation by beta 1 and beta 2 may be compartmentalized or that beta 1 activates cellular mechanisms that offset the well-known cAMP-dependent action on the time course of contraction, Cai transient and on myofilament and sacroplasmic reticulum responsiveness to Ca 2+.