Differential Alterations in Left and Right Ventricular G-Proteins in Congestive Heart Failure due to Myocardial Infarction

In order to examine the status of G-proteins in congestive heart failure due to myocardial infarction, the left coronary artery in rats was ligated and animals assessed after 4, 8 and 16 weeks. Sham-operated control and experimental animals were used for the preparation of membranes from the viable (uninfarcted) left and right ventricles. Adenylyl cyclase activities in the presence of pertussis toxin and cholera toxin were increased and decreased in left ventricles from all groups, respectively. On the other hand, adenylyl cyclase activities in 8 and 16-week experimental right ventricles were unaltered in the presence of pertussis toxin and increased in the presence of cholera toxin. Depression of adenylyl cyclase activities in left ventricles from all groups as well as in the right ventricle at 4 weeks were not evident when enzyme activity was determined in the pertussis toxin-treated membranes in the absence or presence of Gpp(NH)p. Cholera toxin-catalyzed ADP ribosylation was decreased in left ventricles from all infarcted groups and increased in the right ventricles at 8 and 16 weeks whereas the pertussis toxin-catalyzed ADP ribosylation was increased in all experimental tissues except in the right ventricles at 8 and 16 weeks. Gsα-protein content was decreased in the left ventricle at 16 weeks and increased in the right ventricles at 8 and 16 weeks of myocardial infarction. On the other hand, Giα-protein content was increased in left ventricles from all infarcted groups and the 4-week right ventricle but was unaltered in 8 and 16-week right ventricles. An increase in mRNA abundance for Giα-protein was seen in both left and right ventricles following myocardial infarction. A significant increase in mRNA level for Gsα-protein was observed in all left ventricles and 8-week right ventricle following the coronary occlusion. These results suggest that changes in Gs- and Gi-proteins in the failing heart due to myocardial infarction are chamber-specific and are dependent upon the stage of congestive heart failure.