The link between myocardial contraction and relaxation: The effects of calcium antagonists

L. Vittone, H. E. Cingolani, R. A. Mattiazzi

Research output: Contribution to journalArticlepeer-review

Abstract

In isolated rat hearts perfused at constant coronary flow and heart rate the amount of shortening in their major axis (L), the developed tension (T) and their time derivatives (Ĺ and Ṫ) were measured after different interventions. Relative changes of maximal velocities of contraction (+ Ĺ, + Ṫ) and relaxation (- Ĺ, - Ṫ) were assessed by the ratio between both velocities (+Ĺ/-Ĺ, + Ṫ/-Ṫ). After the interventions, cAMP intracellular levels and cAMP dependent protein kinase activity were measured. The negative inotropic effect of verapamil (10-7 m) and nifedipine (5×10-7 m) was accompanied by a relatively greater decrease in maximal velocity of relaxation. Consequently the ratio +Ĺ/-Ĺ increased. Verapamil increased + Ĺ/ - Ĺ from 1.27±0.07 to 1.57±0.08 (P<0.001). Nifedipine increased +Ĺ/-Ĺ from 1.25±0.05 to 1.77±0.12 (P<0.001). Whereas nifedipine increased intracellular cAMP levels from 0.403±0.036 pmol/mg wet weight to 0.534±0.047 (P<0.05), verapamil did not alter them. Neither verapamil nor nifedipine affected cAMP protein kinase activity. Increasing Ca2+ in the perfusate did not change the ratio +Ĺ/-Ĺ. A decrease in extracellular Ca2+, on the other hand, produced a greater decrease in -Ĺ than in +Ĺ, so that the ratio +Ĺ/-Ĺ increased from 1.27±0.05 to 1.49±0.10 (P<0.05). No changes were detected in cAMP levels or its protein kinase activity. Similar results were obtained when + T/-T was analyzed. To offset the negative inotropic effect caused by calcium antagonists, either increased extracellular Ca2+ or isoproterenol can be used. However, for a given inotropic state, relaxation was faster when an increase in cAMP through the beta receptor stimulation was produced to overcome the negative inotropic state. The relatively greater effect of calcium antagonist compounds on relaxation can not be explained by a decrease in cAMP and its protein kinase activity. The mechanism might be related to a lower phospholamban phosphorylation through Ca2+-calmodulin activated protein kinase.

Original languageEnglish (US)
Pages (from-to)255-263
Number of pages9
JournalJournal of Molecular and Cellular Cardiology
Volume17
Issue number3
DOIs
StatePublished - Mar 1985

Keywords

  • Ca-calmodulin activated protein kinase
  • Calcium antagonist compounds
  • Inotropic state
  • Myocardial relaxation
  • Phospholamban phosphorylation
  • cAMP dependent protein kinase

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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