Role of cell contractions in cAMP-induced cardiomyocyte atrial natriureticpeptide release

Incubation of spontaneously beating ventricular cardiomyocytes from neonata l rats with prostaglandin E-2 (0.1 mu M) or forskolin (0.1 mu M) simultaneo usly increased the rate of cellular contraction and atrial natriuretic pept ide (ANP) secretion. Both responses were maximal within 10-20 min of applic ation and were accompanied by three- to fourfold increases in cAMP formatio n. By contrast, a higher regimen of forskolin (10 mu M) promoted a 20- to 3 0-fold increase in basal cAMP production, which was accompanied by the abol ition of contractile activity and ANP release. Low regimens of forskolin (0 .1 mu M) doubled the occurrence of cytosolic Ca2+ transients associated wit h monolayer contraction, whereas higher regimens of forskolin (10 mu M) com pletely suppressed Ca2+ transients. Moreover, in quiescent cultures that we re pretreated with ryanodine, tetrodotoxin, nifedipine, or butanedione mono xime, prostaglandin E-2 (0.1 mu M) and forskolin (0.1 mu M) failed to elici t significant ANP secretion, suggesting that cAMP-elevating agents promote ANP secretion to a great extent via an increase in cellular contraction fre quency in ventricular cardiomyocytes.