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Am J Physiol Heart Circ Physiol 278: H117-H125, 2000;
0363-6135/00 $5.00
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Vol. 278, Issue 1, H117-H125, January 2000

Role of cell contractions in cAMP-induced cardiomyocyte atrial natriuretic peptide release

D. J. Church1, M. C. Rebsamen2, D. Morabito2, V. van der Bent2, M. B. Vallotton2, and U. Lang2

1 Serono, Geneva Pharmaceutical Research Institute, and 2 Division of Endocrinology, University Hospital, CH-1211 Geneva 14, Switzerland

Incubation of spontaneously beating ventricular cardiomyocytes from neonatal rats with prostaglandin E2 (0.1 µM) or forskolin (0.1 µM) simultaneously increased the rate of cellular contraction and atrial natriuretic peptide (ANP) secretion. Both responses were maximal within 10-20 min of application and were accompanied by three- to fourfold increases in cAMP formation. By contrast, a higher regimen of forskolin (10 µM) promoted a 20- to 30-fold increase in basal cAMP production, which was accompanied by the abolition of contractile activity and ANP release. Low regimens of forskolin (0.1 µM) doubled the occurrence of cytosolic Ca2+ transients associated with monolayer contraction, whereas higher regimens of forskolin (10 µM) completely suppressed Ca2+ transients. Moreover, in quiescent cultures that were pretreated with ryanodine, tetrodotoxin, nifedipine, or butanedione monoxime, prostaglandin E2 (0.1 µM) and forskolin (0.1 µM) failed to elicit significant ANP secretion, suggesting that cAMP-elevating agents promote ANP secretion to a great extent via an increase in cellular contraction frequency in ventricular cardiomyocytes.

ventricular cardiomyocytes; cell contractions; prostaglandin E2; forskolin; cytosolic calcium concentration


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