Protective effects of astragaloside IV against hypoxic pulmonary hypertension

Abstract

The present study aimed to evaluate the protective effects of astragaloside IV (As-IV) against hypoxic pulmonary hypertension (HPH) and its mechanisms of action. Sprague-Dawley rats were used in a model of HPH induced by chronic hypoxia. After hypoxia, the mean pulmonary arterial pressure (mPAP), right ventricular pressure (RVP), and right ventricular hypertrophy index (RVHI) were monitored. Relaxation of the pulmonary artery in response to As-IV was measured. The levels of endothelin-1 (ET-1), angiotensin II (Ang II), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in serum were assessed. Cell proliferation was detected by the cell counting kit-8 (CCK-8) assay. Treatment with As-IV significantly decreased mPAP, RVP and RV/(LV + S) and attenuated the development of HPH. Moreover, As-IV time-dependently relaxed the pulmonary arteries from HPH rats. In addition, As-IV decreased the levels of ET-1, Ang II, TNF-α, and IL-6 in serum of HPH rats. In vitro experiments demonstrated that As-IV also significantly inhibited the proliferation of pulmonary artery smooth muscle cells (PASMCs) subjected to hypoxia. Our findings suggested the therapeutic potential of As-IV in the treatment of pulmonary hypertension.