Abstract 243: Mechanism of Statin Prevention Against the Development of Right Ventricular Hypertrophy: Role of Coronary Endothelial Function
We previously reported that a selective right coronary endothelial dysfunction was associated with and actually preceded the development of monocrotaline (MCT) -induced right ventricular hypertrophy (RVH). Statin has been shown to improve vascular endothelial function. In the present study, we investigated if the preservation of coronary endothelial function with statin could abrogate the RVH. Rats were randomly assigned to receive 2mg/kg/day rosuvastatin or placebo in drinking water 1 week before MCT administration. Coronary vasoactivities, right ventricular weight and pressure of the rats were assessed at 3 weeks after MCT. A single 60mg/kg intraperitoneal injection of MCT led to the significant increase in right ventricular pressure and weight in control rats. Statin supplement substantially inhibited this increase. Further investigation of coronary endothelial function revealed a prominent improvement in statin-treated MCT rats as compared to the controls. Isolated rat right coronary arteries showed significantly decreased response to acetylcholine induced endothelium and NO-dependent vasodilation in 3 week MCT control rats (39±2% at 0.3μM vs. 71±7% in normal). However, this response was largely preserved by statin treatment (60±8%). L-NAME constriction, an estimate of spontaneous endothelial NO-mediated dilation, was attenuated in MCT controls (-16±3% vs.-27±2% in normal) but preserved in statin treated rats (-25±3%). Enhanced vasoconstrictory response to U46619, thromboxame analogue, in MCT rats (-21±4% at 30nM vs.-9±2% in normal) was also prevented by statin (-10±0.1%). There were no change in coronary dilatory responses to sodium nitroprusside, a direct NO donor. In the contrast to the early administration of statin, similar supplement given after the development of coronary endothelial functional change could neither reverse coronary endothelial dysfunction nor prevent the RVH. Taken together, our findings indicate a protective role of statin in the prevention against coronary endothelial dysfunction and right heart hypertrophy, and underscore the importance of coronary endothelial dysfunction in the pathogenesis of heart hypertrophy.