Relaxing effect of pharmacologic interventions increasing cAMP in rat heart.

L. Vittone, A. Grassi, L. Chiappe, M. Argel, H. E. Cingolani

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Abstract

The relationship between cAMP and relaxation was studied in the isolated rat heart beating at constant rate and perfused at constant coronary flow. After treatment during 1 min 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 wt to 1.051 +/- 0.099, 0.900 +/- 0.064, and 0.982 +/- 0.138, respectively. Simultaneously glucagon, norepinephrine, and isoproterenol increased cAMP-dependent protein kinase activity ratio from 0.21 +/- 0.02 to 0.45 +/- 0.04, 0.33 +/- 0.02, and 0.34 +/- 0.02, respectively. 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 levels, TTP, or +T/-T. A striking correlation was found between cAMP-dependent protein kinase activity and relaxation induces, i.e., TTP, -T, or +T/-T (r = +/- 0.7 to -0.9). Results suggest that inotropic interventions increasing cAMP levels might be primarily affecting intracellular mechanisms causing relaxation.

Original languageEnglish (US)
JournalThe American journal of physiology
Volume240
Issue number4
StatePublished - Apr 1981
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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    Vittone, L., Grassi, A., Chiappe, L., Argel, M., & Cingolani, H. E. (1981). Relaxing effect of pharmacologic interventions increasing cAMP in rat heart. The American journal of physiology, 240(4).