Beta1-adrenergic receptor activation decreases ANP release via cAMP-Ca2+ signaling in perfused beating rabbit atria

Abstract

Aims: Although a beta-adrenoceptor (beta-AR) blockade-induced increase in plasma atrial natriuretic peptide (ANP) levels is implicated in the therapeutic significance of beta-AR antagonists, the role of beta-AR in the regulation of ANP release is not clearly defined. The purpose of the present study was to define the role of beta-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: beta-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 beta(1)-AR blockade with CGP 20712A but not by beta(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 beta(1)-AR activation decreases ANP release via cAMP- and Ca(2+)-dependent mechanisms.