Simvastatin prevents the development of pulmonary hypertension in the rats through reduction of inflammation

Abstract

To investigate the protection of simvastatin on monocrotaline (MCT)-induce pulmonary hypertension (PH) and the mechanism thereof. Thirty-two male Sprague-Dawley rats were randomly divided into 4 equal groups: PH group undergoing subcutaneous injection of MCT and then gastric infusion of normal saline (NS) once a day for 21 days, simvastatin control group undergoing subcutaneous injection of NS and then gastric infusion of simvastatin 2 microg/g once a day for 21 days, simvastatin intervention group undergoing subcutaneous injection of MTS and then gastric infusion of simvastatin 2 microg/g once a day for 21 days, and control group undergoing subcutaneous injection and gastric infusion of NS. Three weeks later the mean pulmonary arterial pressure (mPAP) was detected by right heart catheter. Then the rats were killed with their lungs taken out. Arterial wall area/vessel area (W/V), and arterial wall thickness/vessel external diameter (T/D) were calculated. Perivascular inflammation was scored with the subjective scale of 0 (no) to 4 (severe). Pulmonary interleukin (IL)-6, tumor necrosis factor alpha (TNF-alpha), and monocyte chemotactic protein 1 (MCP-1) were tested by ELISA. The mPAP of the simvastatin intervention group was (23 +/- 7) mm Hg, significantly lower than that of the PH group [(34 +/- 9) mm Hg, P < 0.05], but not significantly different from that of the normal control group [(20 +/- 4) mm Hg, P > 0.05]. The W/V and T/D of the simvastatin intervention group were 0.442 +/- 0.061 and 0.325 +/- 0.045 respectively, significantly lower than those of the PH group (0.560 +/- 0.086 and 0.368 +/- 0.055 respectively, P < 0.01 and P < 0.05). The perivascular inflammation score of the simvastatin intervention group was (2.19 +/- 0.81), significantly lower than that of the PH group (3.40 +/- 0.65, P < 0.05), and the IL-6, TNF-alpha, and MCP-1 levels of the simvastatin intervention group [(264 +/- 127), (179 +/- 91), and (697 +/- 211) pg/ml respectively] were all significantly lower than those of the PH group [(765 +/- 179), (447 +/- 86), (4428 +/- 757) pg/ml respectively, all P < 0.01]. The protective effects of simvastatin against MCT-induced PH may be associated with the inhibition of the perivascular inflammation and lung IL-6, TNF-alpha, and MCP-1 levels.