Rosiglitazone attenuates monocrotaline-induced pulmonary arterial hypertension in a rat model through activated PPARγ

Abstract

Objective To investigate the protective effects of peroxisome proliferator-activated receptor gamma (PPARγ) and its agonist on monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in rats and the possible molecular mechanisms.Methods Forty Sprague-Dawley (SD) rats were randomly divided into a control group,a rosiglitazone control group,a monocrotaline group and a rosiglitazone intervention group.The rat models of pulmonary hypertension were replicated by subcutaneous injection of monocrotaline (60 mg/kg) by one time in the monocrotaline group and the rosiglitazone intervention group,the other groups were treated with subcutaneous injection of saline.And then rosiglitazone (4.0 mg/kg) was administered by gastric tube in the rosiglitazone control group and rosiglitazone intervention group once daily,at the same time,the control group and monocrotaline group were only administered saline by gastric tube.After 4 weeks,the right ventricular systolic pressure (RVSP) and mean pulmonary aterial pressure (mPAP) were detected by right heart catheter.Right ventricular hypertrophy index (RVHI) was calculated for the assessment of right ventricular hypertrophy.The blood was took from the abdominal aorta for detection of NO and ET-1 levels byELISA and then the lung tissue sections were stained with HE and elastin-van Gieson for histopathological examination and the calculation of tunica media thickness percentage (WT％).Expressions of PPARγ were detected by immunohistochemistry.Results Compared with the monocrotaline group,the mPAP,RVHI and WT％ of rats in rosiglitazone treatment group [(28.2 ± 5.3) mmHg,(0.35 ± 0.05) and (27.7±7.2)％] decreased significantly,but still higher than those of the control group.Rosiglitazone intervention also decreased the plasma ET-1 level (t =3.522,P ＜0.01) and increased the NO level in PAH rats (t =2.363,P ＜0.05),and reversed the hypertrophy of pulmonary artery wall (t =5.192,P ＜ 0.01).Conclusions Rosiglitazone attenuates the pulmonary arterial remodeling in the rat model of monocrotaline-induced pulmonary hypertension and delays the deterioration in PAH through the activation of PPARγ. Key words: Pulmonary arterial hypertension; Rosiglitazone; Monocrotaline; Peroxisome proliferator-activated receptor gamma