Activation of the novel estrogen receptor GPR30 reduces blood pressure and renal injury in the streptozotocin (STZ)‐induced diabetic rat infused with angiotensin II

Abstract

Our previous studies have shown that supplementation with 17‐β estradiol is renoprotective in the STZ‐induced diabetic rat. The aim of this study was to examine if activation of the novel, membrane‐bound estrogen receptor, GPR30, could mediate some of the renoprotective effects of estrogens.Angiotensin II (200 ng/kg/min) was infused via osmotic minipumps from the onset of diabetes (STZ, 50 mg/kg) for 6 weeks. These female diabetic Sprague‐Dawley rats were then either left untreated (D) or were treated with G1 (400 μg/kg/day via minipump), a GPR30 agonist (D+G1) for additional 3 weeks. Urine protein excretion (UPE) was measured before and after G1 treatment, while mean arterial pressure (MAP), blood glucose, glomerulosclerosis (GSI) and glomerular filtration rate (GFR) were assessed only at the end of the study.While no difference in UPE were observed in the D+G1 between baseline and time of sacrifice, UPE was reduced by 40% compared with the untreated D at the time of sacrifice. G1 also reduced MAP by 22% and attenuated glomerulosclerosis without affecting GFR or blood glucose levels.The study suggests that activating the GPR30 receptor is renoprotective in the STZ‐induced diabetic rat infused with Ang II, possibly via lowering MAP. Supported by RO1DK075832 D (n=4) D+G1 (n=5) P value Baseline Sacrifice Baseline Sacrifice UPE (mg/day) 81.4±14.1 133±27.8* 66.2±5.78 77.9±13.7# *0.05 vs Baseline in the same treatment group #0.05 vs. D at sacrifice MAP (mmHg) ‐ 128±8.99 ‐ 100±6.30# Blood glucose (mg/dL) ‐ 348±10.9 ‐ 341±20.7 GFR (ml/min/kidney) ‐ 1.62±0.07 ‐ 1.50±0.09 GSI (AU) ‐ 1.60±0.05 ‐ 1.28±0.08#