Alterations of cardiac ERK1/2 expression and activity due to volume overload were attenuated by the blockade of RAS.

The activities and protein content of extracellular signal-regulated kinase (ERK)1/2 in the heart were measured in rats at 4 and 16 weeks after volume overload due to aortocaval shunt. Protein content of phosphorylated ERK1/2 was increased at both 4 and 16 weeks, whereas protein content of total ERK1/2 was increased only at 16 weeks of inducing volume overload. The ERK1/2 activities, estimated as phospho-Elk-1 content, were also increased at 4 and 16 weeks of inducing volume overload. The increased phosphorylated ERK1/2 and E-26-like (Elk)-1 protein content in 16 weeks failing hearts was much greater than that in 4 weeks hypertrophied hearts. These changes in phosphorylated ERK1/2 and Elk-1 protein content in both 4 and 16 weeks volume overloaded animals were attenuated by treatment with enalapril and/or losartan. The results indicate that activation of ERK1/2 may be involved in the development of cardiac hypertrophy and heart failure due to volume overload, and these changes are partially prevented by blockade of the renin-angiotensin system (RAS).