Chronic Activation of the G Protein-Coupled Receptor 30 with Agonist G-1 Attenuates Heart Failure

Abstract

G protein-coupled receptor (GPR) 30 is a novel estrogen receptor. Recent studies suggest that activation of the GPR30 confers rapid cardioprotection in isolated rat heart. It is unknown whether chronic activation of GPR30 is beneficial or not for heart failure. In this study we investigated the cardiac effect of sustained activation or inhibition of GPR30. Female Sprague-Dawley rats were divided into 7 groups #2Q1: sham surgery (Sham), bilateral ovariectomy (OVX), OVX+estrogen (E2), OVX+isoproterenol (ISO), OVX+ISO+G-1, OVX+ISO+E2+G15, OVX+ISO+E2. ISO (85 mg/kg × 17 day, sc) was given to make the heart failure models. G-1(120 μg/kg·d × 14 day) was used to activate GPR30 and G15 (190 μg/kg·d × 14 day) was used to inhibit GPR30. Concentration of brain natriuretic peptide in serum, masson staining in isolated heart, contractile function and the expression of β1 and β2- adrenergic receptor (AR) of ventricular myocytes were also determined. Our data showed that ISO treatment led to heart failure in OVX rats. G-1 or E2 treatment decreased concentration of brain natriuretic peptide, reduced cardiac fibrosis, and enhanced contraction of the heart. Combined treatment with β1 (CGP20712A) and β2-AR (ICI118551) antagonist abolished the improvement of myocardial function induced by G-1. We also found that chronic treatment with G-1 normalized the expression of β1-AR and increased the expression of β2-AR. Our results indicate that chronic activation of the GPR30 with its agonist G-1 attenuates heart failure by normalizing the expression of β1-AR and increasing the expression of β2-AR. © 2012 Kang et al.