Effects of cyclic GMP and its protein kinase on the contraction of ventricular myocytes from hearts after cardiopulmonary arrest

Jun Su, Peter M. Scholz, James Tse, Harvey R. Weiss

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Hearts undergoing cardiopulmonary arrest and resuscitation have depressed function and may have changes in signal transduction. We hypothesized that the cyclic GMP (cGMP) signaling pathway would be altered in the post-resuscitation heart. This was studied in ventricular myocytes from 7 anesthetized open-chest rabbits. Cardiopulmonary arrest was achieved for 10 min through ventricular fibrillation and respirator shutdown. After cardiopulmonary arrest, respiration was resumed, the heart was defibrillated, and the heart recovered for 15 min. Seven additional rabbits served as controls. Myocyte function was measured via a video edge detector. Myocytes were treated with 8-bromo-cGMP (10 -510-6 mol/L) followed by KT5823 (1(T6 mol/L, cGMP protein kinase inhibitor). The baseline percent shortening was significantly depressed in the cardiac arrest myocytes compared with control (3.3 ± 0.1 vs. 5.5 ± 0.3%). Treatment with 8-Br-cGMP similarly and dose-dependently reduced cell contraction in both cardiac arrest (-24%) and control (-25%) myocytes. The negative effect of 8-Br-cGMP was partially reversed by KT5823 in control myocytes, but not in the arrest group, indicating reduced involvement of cGMP protein kinase. Multiple proteins were specifically phosphorylated when cGMP was present, but the degree of phosphorylation was significantly less in myocytes after cardiac arrest. The data suggested that the basal contraction was reduced, but the functional response to 8-Br-cGMP was preserved in myocytes from cardiopulmonary arrested hearts. The results also indicated that the action of cGMP appeared to be mainly through non-cGMP protein kinase pathways in the post-resuscitation heart.

Original languageEnglish (US)
Pages (from-to)986-992
Number of pages7
JournalCanadian Journal of Physiology and Pharmacology
Volume82
Issue number11
DOIs
StatePublished - Nov 2004

All Science Journal Classification (ASJC) codes

  • Physiology
  • Pharmacology
  • Physiology (medical)

Keywords

  • Cyclic GMP
  • Cyclic GMP protein kinase
  • Myocardial ischemia and reperfusion
  • Myocyte function
  • Rabbit

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