title: Sex differences in ischaemia/reperfusion-induced acute kidney injury depends on the degradation of noradrenaline by monoamine oxidase.
abstract: Ischaemic acute kidney injury (AKI) is a leading killer of both sexes; however, resistance to this injury is higher among women than men. We found that renal venous noradrenaline (NAd) overflow after reperfusion played important roles in the development of ischaemic AKI, and that the attenuation of AKI observed in female rats may be dependent on depressing the renal sympathetic nervous system with endogenous oestrogen. In the present study, we used male and female Sprague-Dawley rats to investigate whether sex differences in the pathogenesis of ischaemic AKI are related to the degradation of NAd by monoamine oxidase (MAO) in the kidney. Ischaemic AKI was achieved by clamping the left renal artery and vein for 45 minutes followed by reperfusion 2 weeks after contralateral nephrectomy. Renal injury was more severe in male rats than in female rats and renal venous plasma NAd levels after reperfusion were markedly elevated in males, but not in females. These sex differences were eliminated by a treatment with isatin, a non-selective MAO inhibitor, and moclobemide, a selective MAOAinhibitor, but not by selegiline, a selective MAOBinhibitor. Ischaemia decreased the mRNA expression levels of both MAOs in the kidney 1 day after reperfusion; however, MAOAmRNA expression levels were higher in female rats than in male rats. These results suggest that the degradation of NAd by MAOAin the kidney contributes to sex differences in the pathogenesis of ischaemia/reperfusion-induced AKI.
authors.affiliation: Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Tanaka
authors.affiliation: Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Yazawa
authors.affiliation: Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Morikawa
authors.affiliation: Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan.|Laboratory of Clinical Pharmacology, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi, Osaka, Japan.
authors.forename: Hidenobu
authors.initials: H
authors.lastname: Tsutsui
authors.affiliation: Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Ohkita
authors.affiliation: Laboratory of Clinical Pharmacology, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi, Osaka, Japan.
authors.forename: Tokihito
authors.initials: T
authors.lastname: Yukimura
authors.affiliation: Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Matsumura
mesh_terms: D000818:Animals; D005260:Female; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D007677:Kidney Function Tests; D008297:Male; D008995:Monoamine Oxidase / Q000235:genetics / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009392:Nephrectomy; D009638:Norepinephrine / Q000097:blood*; D012333:RNA, Messenger / Q000235:genetics; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000097:blood / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D012727:Sex Characteristics
chemical_list: D008996:Monoamine Oxidase Inhibitors; D012333:RNA, Messenger; D008995:Monoamine Oxidase; D009638:Norepinephrine
keywords: acute kidney injury; ischaemia/reperfusion; monoamine oxidase; noradrenaline; sex difference