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However, the effect of microgravity on the kidney and the underlying mechanisms are unknown. In the current study, we used a hindlimb unweighting (HU) animal model to simulate microgravity and employed histological analysis, ischemia\u2013reperfusion experiments, renal ultrasonography, bioinformatics analysis, isometric force measurement, and other molecular experimental settings to evaluate the effects of microgravity on the kidneys and the underlying mechanisms involved in this transition. Relative to controls, 31\u2010day hindlimb unweighting had no obvious effect on serum creatinine and urea nitrogen levels as well as on renal injury scores; however, animals in the HU group showed an impaired renal recovery to ischemia\u2013reperfusion injury. Ultrasonography showed that renal resistive index was increased, which indicated an altered renal hemodynamics induced by simulated microgravity. The enhanced vasoconstriction mediated by the Rho\u2010kinase pathway and impaired vasodilation mediated by NO\u2010eNOS of the intrarenal artery contributed to the altered renal hemodynamics. Simulated microgravity predisposes the kidney to ischemia\u2013reperfusion injury. The altered renal hemodynamics induced by renal arterial remodeling may account for the increased renal injury susceptibility, providing a target for early intervention in kidney dysfunction under microgravity.<\/jats:p>","DOI":"10.1096\/fj.202402267r","type":"journal-article","created":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T11:40:27Z","timestamp":1738064427000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Simulated microgravity predisposes kidney to injury through promoting intrarenal artery remodeling"],"prefix":"10.1096","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-9729-6914","authenticated-orcid":false,"given":"Qiang","family":"Lyu","sequence":"first","affiliation":[{"name":"Department of Nephrology State Key Laboratory of Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, National Clinical Research Center for Kidney Diseases, Nephrology Institute of the 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