β1-Adrenergic receptor activation decreases ANP release via cAMP-Ca2+ signaling in perfused beating rabbit atria

AimsAlthough a β-adrenoceptor (β-AR) blockade-induced increase in plasma atrial natriuretic peptide (ANP) levels is implicated in the therapeutic significance of β-AR antagonists, the role of β-AR in the regulation of ANP release is not clearly defined. The purpose of the present study was to define the role of β-AR subtypes and the mechanisms responsible for regulation of atrial ANP release.Main methodsExperiments were performed in isolated perfused beating rabbit atria, including measurement of atrial contractile response, cAMP efflux, and atrial myocyte ANP release.Key findingsβ-AR activation with (–)-isoproterenol decreased ANP release concomitantly with increases in cAMP efflux concentration, atrial dynamics, stroke volume and pulse pressure in a concentration-dependent manner. The ANP response was inversely related to the change in cAMP efflux concentrations. The isoproterenol-induced decrease in ANP release was inhibited by β1-AR blockade with CGP 20712A but not by β2-AR blockade with ICI 118551. The isoproterenol-induced decrease in ANP release was attenuated by the L-type Ca2+ channel antagonist nifedipine and the cAMP-dependent protein kinase inhibitor KT5720.SignificanceThese findings suggest that β1-AR activation decreases ANP release via cAMP- and Ca2+-dependent mechanisms.