Abstract 041: New Evidence for G Protein-coupled Estrogen Receptor as a Natriuretic Factor

Abstract

Premenopausal women have a lower risk of cardiovascular and renal diseases compared to age-matched men. This protection includes fewer salt-dependent complications. We have shown that female rats have a more robust natriuretic capacity compared to males in response to increased dietary salt. The novel estrogen receptor, G protein-coupled estrogen receptor (GPER), is a membrane-bound receptor linked to acute signaling pathways. GPER activation elicits protective effects throughout the cardiovascular system. However, its role in sodium handling is not defined. We hypothesized that activation of GPER in the renal medulla stimulates sodium excretion. In female Sprague Dawley (SD) rats, isosmotic saline was infused into the renal medullary interstitium (500 μl/h) during a 60-80 min equilibration period and 20 min baseline urine collection period. This was followed by infusion of the GPER agonist G1 (50 pmol/kg/min) or vehicle into the renal medulla for two further 20 min periods. Compared with vehicle, G1 significantly increased urinary sodium excretion and urine flow (from 0.5 ± 0.1 to 0.9 ± 0.2 μmol/min and from 5.3±1.1 to 8.3±1.6 μl/min, respectively, n=6, p<0.05). Urinary potassium excretion and mean arterial pressure remained unchanged during the experiments (0.5 ± 0.1 vs. 0.4 ± 0.1 μmol/min and 108.6 ± 3.4 vs. 107.2 ± 5.1 mmHg, respectively, n=6). Immunohistochemical analysis of GPER revealed more predominant staining in both inner and outer renal medulla in female SD rats, compared to males. GPER appears to be predominantly expressed in interstitial cells. These data reveal that renal medullary GPER plays an important role in renal sodium handling and may account for the enhanced ability to handle increased dietary salt in females. Funded by AHA 15POST25090329 to EYG and P01 HL136267 to DMP