Regulator of G Protein Signaling 2 (RGS2) regulates pulmonary vasoconstriction

Abstract

RGS2 proteins selectively regulate Gq coupled GPCR signaling which inhibits the downstream pathways that causes vasoconstriction and cardiovascular remodeling. RGS2 homozygous knockout (KO) mice have elevated systemic blood pressure associated with enhanced constriction of peripheral blood vessels. Our goal was to determine if RGS2 KO would also cause enhanced constriction of pulmonary blood vessels and cardiac hypertrophy. For our studies we used RGS2 KO and wild‐type (WT) mice. Heart weight to body weight ratio (HW/BW) was used to estimate cardiac hypertrophy. Vascular constriction was measured in pulmonary arteries using precision cut lung slices and videomorphometric analysis of pulmonary artery luminal area. HW/BW ratio was greater in RGS2 KO (5.3 mg/gm) compared to WT (4.6 mg/gm) mice. Dose‐response curves for the Gq coupled GPCR agonists serotonin and U46619 were generated in pulmonary arteries of lung slices from RGS2 KO and WT mice. Maximal constriction caused by serotonin and U46619 was increased by 23% and 18%, respectively, in the RGS2 KO compared to WT mice. Agonist potency in causing constriction was not different. These data show that RGS2 regulates heart weight and GPCR mediated constriction of the pulmonary vasculature and suggests that RGS2 dysregulation may play a role in cardiac and pulmonary vascular disease. Supported by American Asthma Foundation.