Effects of cyclic GMP and its protein kinase on the contraction of ventricular myocytes from hearts after cardiopulmonary arrest.
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(-5)-10(-6) mol/L) followed by KT5823 (10(-6) 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.
Su
Jun
J
Department of Physiology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway 08854-5635, USA.
Scholz
Peter M
PM
Tse
James
J
Weiss
Harvey R
HR
D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism / Q000494:pharmacology*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006323:Heart Arrest / Q000378:metabolism*; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011817:Rabbits; D016276:Ventricular Function
D047428:Protein Kinase Inhibitors; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP