Estrogen protects renal endothelial barrier function from ischemia-reperfusion in vitro and in vivo

Hutchens MP, Fujiyoshi T, Komers R, Herson PS, Anderson S. Estrogen protects renal endothelial barrier function from ischemia-reperfusion in vitro and in vivo. Am J Physiol Renal Physiol 303:F377-F385, 2012. First published May 23, 2012; doi:10.1152/ajprenal.00354.2011.-Emerging evidence suggests that renal endothelial function may be altered in ischemia-reperfusion injury. Acute kidney injury is sexually dimorphic, and estrogen protects renal tubular function after experimental ischemic injury. This study tested the hypothesis that during ischemia-reperfusion, estrogen alters glomerular endothelial function to prevent hyperpermeability. Glomerular endothelial cells were exposed to 8-h oxygen-glucose deprivation (OGD) followed by 4- and 8-h reoxygenation-glucose repletion. After 4-h reoxygenation-glucose repletion, transendothelial permeability to Ficoll-70 was reduced, and transendothelial resistance increased, by 17 beta-estradiol vs. vehicle treatment during OGD (OGD-vehicle: 91.0 +/- 11.8%, OGD-estrogen: 102.6 +/- 10.8%, P < 0.05). This effect was reversed by coadministration of G protein-coupled receptor 30 (GPR30) antagonist G15 with 17 beta-estradiol (OGD-estrogen-G15: 89.5 +/- 6.9, P < 0.05 compared with 17 beta-estradiol). To provide preliminary confirmation of this result in vivo, Ficoll-70 was administered to mice 24 h after cardiac arrest and cardiopulmonary resuscitation (CA/CPR). Blood urea nitrogen (BUN) and serum creatinine (SCr) in these mice were elevated within 12 h following CA/CPR and reduced at 24 h by pretreatment with 17 beta-estradiol (BUN/SCr 17 beta-estradiol: 34 +/- 19/0.2 +/- 0.1 vehicle: 92 +/- 49/0.5 +/- 0.3, n = 8-12, P < 0.05). Glomerular sieving of Ficoll 70 was increased by CA/CPR within 2 h of injury and 17 beta-estradiol treatment (theta; 17 beta-estradiol: 0.74 +/- 0.26 vs. vehicle: 1.05 +/- 0.53, n = 14-15, P < 0.05). These results suggest that estrogen reduces postischemic glomerular endothelial hyperpermeability at least in part through GPR30 and that estrogen may regulate post CA/CPR glomerular permeability in a similar fashion in vivo.