Abstract: FR-OR072
Activation of G Protein-Coupled Estrogen Receptor Ameliorates Proteinuria in Dahl Salt-Sensitive Female Rats
Session Information
- Hypertension and CVD: Mechanisms
November 08, 2019 | Location: 206, Walter E. Washington Convention Center
Abstract Time: 04:42 PM - 04:54 PM
Category: Hypertension and CVD
- 1403 Hypertension and CVD: Mechanisms
Authors
- Gohar, Eman Y., University of Alabama at Birmingham, Birmingham, Alabama, United States
- Almutlaq, Rawan N., University of Alabama at Birmingham, Birmingham, Alabama, United States
- De Miguel, Carmen, University of Alabama at Birmingham, Birmingham, Alabama, United States
- Daugherty, Elizabeth M., University of Alabama at Birmingham, Birmingham, Alabama, United States
- Jin, Chunhua, University of Alabama at Birmingham, Birmingham, Alabama, United States
- Pollock, Jennifer S., University of Alabama at Birmingham, Birmingham, Alabama, United States
- Pollock, David M., University of Alabama at Birmingham, Birmingham, Alabama, United States
Background
Recent evidence implicates a central role for the G protein-coupled estrogen receptor (GPER) in the maintenance of cardiovascular and renal health in women. The current study tested whether GPER activation ameliorates salt-induced elevation in blood pressure and renal damage in female Dahl salt-sensitive (SS) rats.
Methods
12-14 weeks old female rats were implanted with telemetry transmitters and osmotic minipumps releasing G1 (GPER agonist, 400 μg/kg/day, IP) or its vehicle for 28 days. Two weeks after pump implantation, rats were shifted from a normal salt diet (NS, 0.4% NaCl, AIN-76A Purified Rodent Diet) to a matched high salt diet (HS, 4% NaCl) for two weeks. 24-hour urine samples were collected while on NS and HS diets.
Results
24-hr mean arterial pressure (MAP) markedly increased in response to HS in vehicle-treated rats in comparison to NS baseline values (141±3 vs. 124±1 mmHg, respectively, n=5, p<0.05). This salt sensitivity was evident also in G1-treated rats (MAP: 144±4 vs. 124±2 mmHg, n=6). No differences were observed in diastolic, systolic blood pressure, heart rate or locomotor activity between G1- and vehicle-treated rats. Body weight, food intake, water intake, urine flow and urinary sodium excretion were not significantly altered by G1. HS significantly increased urinary excretion of protein, albumin, nephrin (podocyte damage marker) and KIM-1 (proximal tubule injury marker) in vehicle-treated rats, compared to NS (protein: 63.9±16.2 vs. 22.8±3.8 mg/day, albumin: 52.6±19.9 vs. 12.4±5.1 mg/day, nephrin: 65.9±8.7 vs. 16.4±5.3 ng/day, KIM-1: 30.2±7.2 vs. 16.6±1.7 ng/day, n=7, p<0.05). Importantly, GPER activation prevented HS-induced proteinuria, albuminuria and increase in KIM-1 excretion (n=6, p<0.05), but not nephrinuria suggesting that systemic GPER activation protects against HS-induced proximal tubular damage in female Dahl SS rats.
Conclusion
Collectively, we found that GPER activation ameliorates salt-induced renal damage, but not salt sensitive hypertension, in female Dahl SS rats. Our data suggest that GPER elicits a protective effect against HS-induced renal damage, specifically proximal tubular damage, in a blood pressure-independent manner.
Funding
- Other NIH Support