Early activation of p160ROCK by pressure overload in rat heart

We investigated the effects of acutepressure overload on activation of p160^ROCK in ratmyocardium. Constriction of transverse aorta, controlled to increasepeak systolic pressure of ascending aorta by ~40 mmHg, induced arapid association of RhoA with Dbl-3 and p160^ROCK. Thebinding of p160^ROCK to RhoA was rapidly increased, peakingat 30 min (~3.5-fold), but reduced to lower levels (~1.9-fold) by60 min of pressure overload. The activity of immunoprecipitatedp160^ROCK toward myosin light chain increased ~2.5-foldwithin 10 min but decreased to lower levels (~1.6-fold) after 60 minof pressure overload. Confocal microscopic analysis indicated thatpressure overload induced the formation of aggregates ofp160^ROCK and RhoA along the longitudinal axis of cardiacmyocytes. Immunoelectron microscopic analysis showed that pressureoverload induced the association of p160^ROCK and RhoA toZ-line, T-tubule, and subsarcolemmal areas. The rapid activation ofp160^ROCK by pressure overload and its aggregation insubcellular structures involved in transmission of mechanical forcesuggest a role for this enzyme in the mechanobiochemical transductionin the myocardium.