Beta1‐Adrenoceptor activation decreases atrial myocytic ANP release via cAMP‐protein kinase signaling

Abstract

Although beta-adrenergic receptor (AR) blockade-induced increase in plasma atrial natriuretic peptide (ANP) levels is implicated in the therapeutic significance of beta-AR blockade, the role of beta-AR in the regulation of atrial ANP release is not clearly defined. The purpose of the present study was to define the role of beta-AR subtypes in the regulation of atrial ANP release. Experiments were performed in perfused beating rabbit atria allowing measurements of atrial contractile response, cAMP efflux and atrial myocytic ANP release. beta-AR activation with (-) isoproterenol (ISO) decreased atrial myocytic ANP release concomitantly with increases in cAMP efflux concentration and atrial pulse pressure in a concentration-dependent manner. The ANP response was inversely related to the change in cAMP efflux concentration. ISO-induced decrease in ANP release was blocked by beta 1-AR blockade with CGP20712A but not by beta 2-AR with ICI118551. ISO-induced change in ANP release was attenuated by staurosporine, an inhibitor of nonselective protein kinase. These findings suggest that beta 1-AR activation decreases atrial myocytic ANP release via adenylyl cyclase-cAMP-protein kinase signaling pathway. Supported by KOSEF (R01-2003-000-10507-0).