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Sex differences in ischaemia/reperfusion‐induced acute kidney injury depends on the degradation of noradrenaline by monoamine oxidase
Author(s) -
Tanaka Ryosuke,
Yazawa Maki,
Morikawa Yuri,
Tsutsui Hidenobu,
Ohkita Mamoru,
Yukimura Tokihito,
Matsumura Yasuo
Publication year - 2017
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12713
Subject(s) - kidney , medicine , endocrinology , pathogenesis , acute kidney injury , ischemia , monoamine oxidase , selegiline , monoamine oxidase a , chemistry , serotonin , receptor , enzyme , biochemistry , disease , parkinson's disease
Summary 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 ( NA d) 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 NA d 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 NA d 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 MAO A inhibitor, but not by selegiline, a selective MAO B inhibitor. Ischaemia decreased the mRNA expression levels of both MAO s in the kidney 1 day after reperfusion; however, MAO A mRNA expression levels were higher in female rats than in male rats. These results suggest that the degradation of NA d by MAO A in the kidney contributes to sex differences in the pathogenesis of ischaemia/reperfusion‐induced AKI.