β 1-Adrenergic receptor activation decreases ANP release via cAMP-Ca 2+ signaling in perfused beating rabbit atria

Abstract

Aims Although 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 methods Experiments were performed in isolated perfused beating rabbit atria, including measurement of atrial contractile response, cAMP efflux, and atrial myocyte ANP release. Key findings β-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 β 1-AR blockade with CGP 20712A but not by β 2-AR blockade with ICI 118551. The isoproterenol-induced decrease in ANP release was attenuated by the L-type Ca 2+ channel antagonist nifedipine and the cAMP-dependent protein kinase inhibitor KT5720. Significance These findings suggest that β 1-AR activation decreases ANP release via cAMP- and Ca 2+-dependent mechanisms.