ABSTRACT
Objective To investigate the effects and mechanism of pitavastatin on monocrotaline ( MTC )-induced pulmonary arterial hypertension ( PAH) in rats. Methods A total of 50 male Sprague-Dawley rats were randomly divided into five groups (n=10 each):pitavastatin treatment at low dose (1 mg·kg-1·d-1),treatment at high dose (3 mg·kg-1·d-1), pitavastatin prevention regimen (1 mg·kg-1·d-1), model control group, and the normol control group. PAH was induced by applying a single subcutaneous injection of MTC(55 mg·kg-1)in the first four groups of rats. The treatment lasted for 8 weeks. At the end of the study, survival rates and mean pulmonary arterial pressure ( mPAP ) among groups were compared. The expression levels of platelet-derived growth factor-B ( PDGF-B) and IL-6, Rac1 mRNA in small pulmonary artery were also detected. Results All rats in the prevention protocol and normal control group survived. Pitavastatin treatment improved survival in the treatment protocol(P<0. 01). The survival rate in the low dose, high dose, and model control group was 60. 0%, 80. 0%, and 40. 0%, respectively. Pitavastatin in both prevention or treatment protocol significantly lowered mPAP (P<0. 01). Pitavastatin also inhibited PDGF-B and IL-6 expression (P<0. 01),and inhibited Rac1 mRNA expression in lung tissues (P<0. 01). Conclusion Pitavastatin reduces mPAP in the MTC-induced PAH rat model, the mechanism of which may be related to inhibition of Rac1 expression,smooth muscle cell proliferation and inflammatory mediator IL-6.