Early activation of p160ROCK by pressure overload in rat heart

We investigated the effects of acute pressure overload on activation of p160(ROCK) in rat myocardium. Constriction of transverse aorta, controlled to increase peak systolic pressure of ascending aorta by similar to40 mmHg, induced a rapid association of RhoA with Dbl-3 and p160(ROCK). The binding of p160(ROCK) to RhoA was rapidly increased, peaking at 30 min ( similar to 3.5- fold), but reduced to lower levels ( similar to 1.9- fold) by 60 min of pressure overload. The activity of immunoprecipitated p160(ROCK) toward myosin light chain increased similar to 2.5-fold within 10 min but decreased to lower levels ( similar to 1.6-fold) after 60 min of pressure overload. Confocal microscopic analysis indicated that pressure overload induced the formation of aggregates of p160(ROCK) and RhoA along the longitudinal axis of cardiac myocytes. Immunoelectron microscopic analysis showed that pressure overload induced the association of p160(ROCK) and RhoA to Z-line, T-tubule, and subsarcolemmal areas. The rapid activation of p160(ROCK) by pressure overload and its aggregation in subcellular structures involved in transmission of mechanical force suggest a role for this enzyme in the mechanobiochemical transduction in the myocardium.