Abstract
Statins, HMG CoA reductase inhibitors, have pleiotropic effects on vascular diseases. We therefore investigated whether simvastatin ameliorates the development of pulmonary hypertension(PH) and vascular changes in the monocrotaline(MCT)-treated rats. Methods: Rats treated with a single subcutaneous injection of MCT(60mg/kg) or saline, were injected intraperitoneally with simvastatin(10mg/kg) or saline once daily from day –3 to day 16. At the end of experiment, awake mean pulmonary arterial pressure was determined through pulmonary artery catheter. The heart was dissected to weigh the right ventricle, and the lungs were obtained for vascular mophometric analysis. To correlate VCAM1 expression to the vasculoprotective effects of simvastatin, immunohistochemical study was performed. Results: MCT rats developed PH, right ventricular hypertrophy(RVH) and pulmonary vascular disease, which was accompanied by upregulation of VCAM1 expression. Simvastatin decreased PH , RVH, pulmonary arterial wall thickness and the proportion of muscular arteries in the peripheral arteries, which was associated with suppression of VCAM1 expression. Conclusion: Simvatatin ameliorated the vascular changes associated with PH in rats. These findings suggest that simvastatin could be a new therapeutic agent against PH at least in part by modifying oxidant-related signaling pathways. [Jpn J Physiol 54 Suppl:S250 (2004)]
