Relaxant effect of pharmacological interventions increasing heart cyclic AMP and its protein kinase

After 1 min of treatment with different positive inotropic interventions, cyclic nucleotide levels (cAMP and cGMP) and cAMP-dependent protein kinase activity were determined in heart homogenates. Glucagon, norepinephrine, and isoproterenol increased cAMP from 0.503 +/- 0.025 pmol/mg wet weight to 1.051 +/- 0.099, 0.900 +/- 0.064, and 0.982 +/- 0.138, respectively. Simultaneously, cAMP-dependent protein kinase activity ratio rose from 0.21 +/- 0.02 to 0.45 +/- 0.04 with glucagon, 0.33 +/- 0.02 with norepinephrine, and 0.34 +/- 0.02 with isoproterenol. The ratio between maximal velocities of contraction and relaxation (+T/-T) was significantly decreased by these interventions, whereas time to peak tension (TTP) was shortened by norepinephrine and isoproterenol. High calcium, ouabain, and paired stimulation did not affect cAMP-dependent protein kinase activity and +T/-T. Our results suggest that inotropic interventions increasing cAMP levels might primarily affect intracellular mechanisms causing relaxation.