Genistein attenuates monocrotaline-induced pulmonary arterial hypertension in rats by activating PI3K/Akt/eNOS signaling

Abstract

Introduction: Phytoestrogen genistein may be useful to treat pulmonary arterial hypertension (PAH). However, its mechanism is still not clear. The aim of the present study was to confirm the therapeutic effects of phytoestrogen genistein on PAH in monocrotalineinduced rat model and to explore its mechanism. Materials and Methods: Sprague-Dawley male rats were randomly divided into 4 groups: control group (n=8), PAH group (n=8), genistein treament group with three different doses (n=8 in each dose group) and group of PI3K inhibitor LY294002. The rat model of PAH was induced by monocrotaline (MCT). The situation of survival of rats was observed. Pathological studies of lung and heart tissues were performed. Western-blot detection of P-Akt and P-eNOS expression levels in lung tissue was carried out. Nitrate reductase analysis was used to measure nitric oxide (NO) in lung tissue. Results: Genistein treatment resulted in significant improvement in the speed of tricuspid regurgitation, diameter of pulmonary artery, mean pulmonary artery pressure and right ventricular hypertrophy index. Genistein treatment also resulted in significant improvement in the stenosis of pulmonary artery, proliferation of smooth muscle, right ventricular hypertrophy and myocardial hypertrophy. These therapeutic effects were more obvious with increasing dose of genistein. After genistein treatment, amelioration