We recently reported that increased vascular endothelial NO production could protect against the development of monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) and right ventricular hypertrophy (RVH) in rats. Present study investigated whether the pleiotropic action of HMG-CoA reductase inhibitors in upregulating endothelial function could also protect against the MCT-induced end organ damages. Rosuvastatin (2 mg/kg/day via oral gavage) or placebo was initiated 1 week before or 1 week after MCT (60 mg/kg, i.p.) administration. One month after MCT, significant PAH developed in the placebo rats, which were accompanied by histological evidence of pulmonary vascular thickening and right ventricular hypertrophy. The coronary endothelial vasodilatory function, assessed with endothelial/NO-dependent responses to acetylcholine and L-NAME, were depressed while the constrictory responses to known coronary constrictors enhanced. In rats received rosuvastatin treatment one week prior to MCT administration, a significant reduced PAH and RVH was observed, as well as reduced pulmonary vascular and right ventricular remodelings. Rosuvastatin one-week post-treatment had no effect on PAH but inhibited RVH. Right coronary endothelial dysfunction, which was shown in placebo rats, was effectively prevented by both pre- and post- rosuvastatin treatment, while this effect was more dramatic in pre-treated group. Left coronary endothelial function, which was not affected by MCT, also showed an upregulation by rosuvastatin. Taken together, our results demonstrated the pleiotropic protection of rosuvastatin against the development of PAH and RVH, confirmed our previous finding that the targeted preservation of coronary endothelial function and vasoactivity may provide a novel approach to protect against cardiac remodeling.