title: Estrogen protects renal endothelial barrier function from ischemia-reperfusion in vitro and in vivo.
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 reoxygenation-glucose repletion. After 4-h reoxygenation-glucose repletion, transendothelial permeability to Ficoll-70 was reduced, and transendothelial resistance increased, by 17β-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 17β-estradiol (OGD-estrogen-G15: 89.5 ± 6.9, P < 0.05 compared with 17β-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 17β-estradiol (BUN/SCr 17β-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 17β-estradiol treatment (θ; 17β-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.
authors.affiliation: Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, OR 97239, USA. hutchenm@ohsu.edu
authors.forename: Michael P
authors.initials: MP
authors.lastname: Hutchens
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Fujiyoshi
authors.forename: Radko
authors.initials: R
authors.lastname: Komers
authors.forename: Paco S
authors.initials: PS
authors.lastname: Herson
authors.forename: Sharon
authors.initials: S
authors.lastname: Anderson
mesh_terms: D000818:Animals; D002460:Cell Line; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D060730:Glomerular Filtration Barrier / Q000187:drug effects*; D005947:Glucose / Q000172:deficiency; D000860:Hypoxia / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010052:Ovariectomy; D060888:Real-Time Polymerase Chain Reaction; D011960:Receptors, Estrogen / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*
chemical_list: D004967:Estrogens; D005353:Fibronectins; D005456:Fluorescent Dyes; D011960:Receptors, Estrogen; D004958:Estradiol; D016650:Fluorescein-5-isothiocyanate; D005947:Glucose