Ginsenoside Rb1 Attenuates Pulmonary Arterial Contraction to Agonist via Inhibiting Store‐operated Calcium Entry in Control and Pulmonary Hypertension Rats

Abstract

This study was designed to investigate the effects and mechanisms of ginsenoside Rb1 on pulmonary arteries (PAs) and pulmonary arterial smooth muscle cells (PASMCs) in control and pulmonary hypertension (PH) rats. Isometric tension inPAs, intracellular Ca2+ concentration ([Ca2+]i) and Mn2+ quenching of Fura‐2 in the PASMCs f were measured from control and two widely used models of chronic hypoxia (CH)‐ and monocrotaline (MCT)‐induced PH rats. The results showed that ginsenoside Rb1‐induced dose‐dependent relaxation (0.1‐300 µM, EC50=6 µM ) on PAs precontracted with endothelin‐1 (ET‐1) of control rats. Pretreatment with 6 μM ginsenoside Rb1 attenuated PAs contraction induced by a store‐operated calcium entry (SOCE) activator, 10μM cyclopiazonic acid (CPA) and 10 nM ET‐1 on control, CH‐ and MCT‐treated rats, respectively. 6 μM Ginsenoside Rb1 also induced vasorelaxation of PAs precontracted with 10μM CPA and 10 nM ET‐1 on control, CH‐exposed and MCT‐treated rats, respectively. Moreover, after a SOCE blocker, 20 nM Gd3+ decreased pre contraction induced by 10 nM ET‐1, 6 μM ginsenoside Rb1 can not significantly reduce the PAs contraction again. 6 μM ginsenoside Rb1 significantly decreased 10μM CPA‐induced Ca2+ transients and cation entry by Mn2+ quenching in PASMCs of control, CH‐ and MCT‐ groups. We concluded that ginsenoside Rb1 may take a PAs relaxation via inhibiting SOCE on control, CH‐exposed and MCT‐treated rats. The vasorelaxation of ginsenoside Rb1 in CH‐ and MCT‐induced PH rats may provide a new insight for curing PH.