C-type natriuretic peptide inhibits ANP secretion and atrial dynamics in perfused atria: NPR-B-cGMP signaling

The purpose of the present experiments was to define the role of C-type nat riuretic peptide (CNP) in the regulation of atrial secretion of atrial natr iuretic peptide (ANP) and atrial stroke volume. Experiments were performed in perfused beating and nonbeating quiescent atria, single atrial myocytes, and atrial membranes. CNP suppressed in a dose-related fashion the increas e in atrial stroke volume and ANP secretion induced by atrial pacing. CNP c aused a right shift in the positive relationships between changes in the se cretion of ANP and atrial strobe volume or translocation of the extracellul ar fluid (ECF), which indicates the suppression of atrial myocytic release of ANP into the paracellular space. The effects of CNP on the secretion and contraction were mimicked by 8-bromoguanosine 3',5'-cyclic monophosphate ( 8-BrcGMP). CNP increased cGMP production in the perfused atria, and the eff ects of CNP on the secretion of ANP and atrial dynamics were accentuated by pretreatment with an inhibitor of cGMP phosphodiesterase, zaprinast. An in hibitor of the biological natriuretic peptide receptor (NPR), HS-142-1, att enuated the effects of CNP. The suppression of ANP secretion by CNP and 8-B rcGMP was abolished by a depletion of extracellular Ca2+ in nonbeating atri a. Natriuretic peptides increased cGMP production in atrial membranes with a rank order of potency of CNP > BNP > ANP, and the effect was inhibited by HS-142-1. CNP and 8-BrcGMP increased intracellular Ca2+ concentration tran sients in single atrial myocytes, and mRNAs for CNP and NPR-B were expresse d in the rabbit atrium. From these results we conclude that atrial ANP rele ase and stroke volume are controlled by CNP via NPR-B-cGMP mediated signali ng, which may in turn act via regulation of intracellular Ca2+.