Simvastatin prevents ERK activation in myocardial hypertrophy of spontaneously hypertensive rats

Background. Statins exert regression of left ventricular hypertrophy independent of their plasma cholesterol-lowering actions. However, the underlying mechanism is not clear. Methods. We tested the hypothesis that the extracellular signal-regulated kinases (ERKs) signaling pathway could be a target of simvastatin (SIM) and involved in SIM-induced LVH regression in spontaneously hypertensive rats (SHR). Fourteen 14-week old-SHR males were randomly divided into a SHR SIM group (n = 7) or a SHR control group (n = 7). The SHR SIM group was given SIM 40 mg/kg . d via injection ig, while the SHR control group was routinely given only vehicle (0.5% carboxymethyl cellulose ig). Seven Wistar Kyoto rats served as normal controls. Results. Ten weeks of treatment with SIM in SHR had no influence on blood pressure. The ratio of left ventricle weight to body weight in the SHR SIM group was decreased significantly compared to that in the SHR control group (p < 0.05). Among the three groups there was no significant difference in total ERK expression (p > 0.05). SIM treatment caused a significant reduction in the expression of phosphorylated-ERK, the kinase activity of ERK, the levels of mitogen-activated protein kinase phosphatase-1 protein and its mRNA (p < 0.01 for all). Conclusions. The Hydroxymethylglutaryl coenzyme A reductase inhibitor SIM prevents the activation of ERK in SHR to mediate regression of myocardial hypertrophy in SHR.