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

Michael P. Hutchens, Tetsuhiro Fujiyoshi, Radko Komers, Paco S. Herson, Sharon Anderson

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

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 reoxygen-ation-glucose repletion. After 4-h reoxygenation-glucose repletion, transendothelial permeability to Ficoll-70 was reduced, and transen-dothelial resistance increased, by 17(3-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(3-estra-diol (OGD-estrogen-G15: 89.5 ± 6.9, P < 0.05 compared with 17(3-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(3-estradiol (BUN/SCr 17(3-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(3-estradiol treatment (0; 17(3-estradiol: 0.74 ± 0.26 vs. vehicle: 1.05 ± 0.53, n = 14-15, P < 0.05). These results suggest that estrogen reduces post-ischemic 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.

Original languageEnglish (US)
Pages (from-to)F377-F385
JournalAmerican Journal of Physiology - Renal Physiology
Volume303
Issue number3
DOIs
StatePublished - Aug 1 2012

Keywords

  • Acute kidney injury
  • Acute renal failure
  • Cardiac arrest
  • Cardiopulmonary resuscitation
  • Estradiol
  • Estrogen
  • Gender
  • Ischemia-reperfusion injury
  • Oxygen-glucose deprivation
  • Renal ischemia
  • Sex

ASJC Scopus subject areas

  • Physiology
  • Urology

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