Protective effects of melatonin against kidney injury of renovascular hypertensive rats and related mechanisms

Objective To investigate the protective effects of melatonin（MT） against kidney injury in reno-hypertensive rats（two kidneys one clip model,2K1C） and relevant mechanisms.Methods Renovascular hypertension was induced in male Wistar rats by the two-kidney one-clip（2K1C） method.The model rats were randomized into untreated 2K1C group and MT-treated 2K1C group（n=8,respectively）.Another 8 rats were selected as controls in the sham operation group.After 8 weeks of follow-up,we monitored their blood pressure.Kidney histological changes were examined by hematoxylin and eosin（HE） staining.Renal superoxide dismutase（SOD） activity and malondialdehyde（MDA） contents were detected by colorimetric method.The expressions of inducible nitric oxide synthase（iNOS） and endothelial nitric oxide synthase（eNOS） in renal tissue were detected by immunohistochemistry and semi-quantitative reverse transcription-polymerase chain reaction（RT-PCR）,respectively.Results ① Four weeks after surgery,increased aortic pressure was present in 2K1C rats as compared with those in the sham operation group,and treatment with MT attenuated the increase（all P＜0.05）.② Rats subjected to 2K1C displayed markedly worsened renal histological changes compared with sham controls.In contrast,MT significantly attenuated morphological damage（all P＜0.01）.③ 2K1C hypertension resulted in increased MDA content and decreased SOD activity.MT pretreatment significantly reversed the above changes.④ Renal iNOS expression was up-regulated in 2K1C rats,while eNOS expression significantly down-regulated.MT inhibited the upregulation of iNOS and the downregulation of eNOS in the clipped kidneys of 2K1C rats.Conclusion Melatonin could exert protection BHDWG6,WK49ZQ0Wagainst hypertension-induced renal tubulointerstitial injury,at least partly,by inhibiting iNOS expression and increasing eNOS expression.