Abstract 13967: Role of PKC, PKG and Actin-Myosin Interaction in the Adaptive Diastolic Response to Acute Stretch
Objectives: Myocardial stretch elicits an adaptive diastolic response characterized by a progressive decrease in myocardial stiffness. We aimed to better understand the role of PKC, PKG and actin-myosin interaction in this response under basal and ischemic conditions.
Methods: Rabbit papillary muscles were acutely stretched from 92% to 100% of Lmax in a modified Krebs-Ringer solution in the (A) absence (n=9) or presence of (B) chelerythrine (an inhibitor of PKC, n=7), (C) Rp-8-Br-PET-cGMPs (an inhibitor of PKG, n=7), (D) chelerythrine and Rp-8-Br-PET-cGMPs (n=8), (E) PMA (an agonist of PKC, n=7). Group F was stretched during ischemia (n=7) and other protocols were performed in the ischemic setting in the presence of (G) 8-Bromo-cGMP (an agonist of PKG, n=7), (H) PMA (n=7), (I) BDM (an inhibitor of actin-myosin interaction, n=8) and (J) 8-Bromo-cGMP and BDM (n=7). Results are presented as mean±standard error of mean (P<0.05).
Results: In the basal setting, the inhibition of PKC or PKG blunted the decrease in passive tension (PT) observed 15 minutes after stretch in group A (46.2±1.8%) to 26.3±1.1% and 34.5±2.7%, respectively. The presence of PMA attenuated the increase in PT observed immediately upon stretch (1219±173% in group A versus 485±118% in group E). During ischemia, the presence of an agonist of PKG promoted a decrease in PT of 20.6±3.2% in the 15 minutes following acute stretch (contrasting with an increase of 16.6±15.7% in group F during the same period). However, the presence of PMA did not alter the diastolic response to stretch of the ischemic myocardium. In the presence of BDM, stretching the muscles during ischemia elicited a decrease in PT of 28.6±1.0% (15 minutes after stretch), while the simultaneous presence of 8-Bromo-cGMP and BDM promoted a decrease in PT of 28.3±1.5% during the same period.
Conclusion: Our results allow a better understanding of the role of PKC as an acute modulator of myocardial stiffness during an hemodynamic overload. PKG is also an active player in the adaptive diastolic response to stretch, promoting a decrease in myocardial stiffness in the overloaded ischemic heart. Finally, disturbed actin-myosin interaction was also an important contributor to diastolic dysfunction in the stretched ischemic myocardium.
- © 2011 by American Heart Association, Inc.