Effects Of CAMP And Its Raising Agents On Atrial ANP Secretion In Beating Rabbit Atria

Regulation of atrial secretion of atrial natriuretic peptide (ANP) is coupled to changes in atrial dynamics. However, the mechanism by which mechanical stretch or release controls myocytic ANP secretion has remains to be defined. The purpose of the present study was to define the role of adenosine 3',5' -cyclic monophosphate (cAMP) in the regulation of atrial dynamics and atrial myocytic ANP release in the beating rabbit atria. Increase in pacing frequency increased ANP secretion and the concentration of ANP in perfuate in terms of extracellular fluid (ECF) translocation with concomitant changes in atrial stroke volume and ECF translocation. cAMP-raising agents, isoproterenol (1.0 nM), forskolin (1.0 μM), a direct activator of adenylyl cyclase (AC), 3-isobutyl-1-methylxanthine (1.0 mM), a non-specific cyclic nucleotide phosphodiesterases (PDE) inhibitor, and 8-bromo adenosine 3',5'-cyclic monophosphate (8-Br cAMP, 0.5 mM), a permeable cell membrane cAMP analog, inhibited ANP secretion and the concentration of ANP with increased atrial dynamics. cAMP-raising agents and cAMP analog shifted the relationships between ANP secretion and atrial stroke volume, ANP secretion and ECF translocation, and atrial stroke volume and ECF translocation to downward and rightward, which indicated that cAMP inhibits of atrial release of ANP secretion. Diltiazem, a blocker of L-type Ca²⁺ channel, inhibited the forskolin-induced increase in atrial dynamics, but failed to modulate the effect of forskolin-induced decrease of ANP release. The non-selective inhibitor of protein kinases staurosporine blocked forskolin-induced inhibition of ANP release in dose-dependent manner. Sataurosporine shifted the relationships between cAMP and ANP release. These results suggest that cAMP inhibits atrial myocytic release of ANP via protein kinase-dependent and L-type Ca²⁺ channel-dependent and -independent signaling pathways.