title: Protective effect of 17β-estradiol on ischemic acute kidney injury through the renal sympathetic nervous system.
abstract: Enhanced renal sympathetic nerve activity during an ischemic period and renal venous norepinephrine overflow after reperfusion play important roles in the development of ischemic acute kidney injury. In this study, we examined the effect of 17β-estradiol on the renal sympathetic nervous system and kidney function in ischemia/reperfusion-induced acute kidney injury in anesthetized rats. Ischemic acute kidney injury was induced by clamping the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after a contralateral nephrectomy. Intravenous injection of 17β-estradiol (100 μg/kg) 15 min before reperfusion suppressed enhanced renal sympathetic nerve activity during renal ischemia, also suppressed renal venous norepinephrine overflow after reperfusion, and attenuated ischemia/reperfusion-induced renal dysfunction with histological damage. The above renoprotective effects of 17β-estradiol were reversed by pretreatment with tamoxifen (5 mg/kg), an estrogen receptor antagonist, or N(G)-nitro-L-arginine methyl ester (0.3 mg/kg), a non-selective nitric oxide synthase inhibitor. These results indicate that 17β-estradiol can suppress enhanced renal sympathetic nerve activity during renal ischemia, and its consequent effect on norepinephrine overflow from nerve endings, by nitric oxide production via estrogen receptors. These effects appear to contribute to renoprotection against ischemia/reperfusion-induced renal injury.
authors.affiliation: Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Tanaka
authors.forename: Hidenobu
authors.initials: H
authors.lastname: Tsutsui
authors.forename: Shuhei
authors.initials: S
authors.lastname: Kobuchi
authors.forename: Takahiro
authors.initials: T
authors.lastname: Sugiura
authors.forename: Masayo
authors.initials: M
authors.lastname: Yamagata
authors.forename: Mamoru
authors.initials: M
authors.lastname: Ohkita
authors.forename: Masanori
authors.initials: M
authors.lastname: Takaoka
authors.forename: Tokihito
authors.initials: T
authors.lastname: Yukimura
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Matsumura
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000008:administration & dosage / Q000627:therapeutic use*; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000008:administration & dosage / Q000627:therapeutic use*; D007275:Injections, Intravenous; D007511:Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009638:Norepinephrine / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D051437:Renal Insufficiency / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D012082:Renal Veins; D015427:Reperfusion Injury / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D004965:Estrogen Antagonists; D004967:Estrogens; D013629:Tamoxifen; D004958:Estradiol; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine