Losartan protects against intermittent hypoxia-induced peritubular capillary loss by modulating the renal renin-angiotensin system and angiogenesis factors

• 来源期刊: 生物化学与生物物理学报（英文版）
• 关键词: obstructive sleep apnea chronic intermittent hypoxia renal peritubular capillary loss angiogenesis factor losartan
• 年，卷（期）: 2020,（1）
• 页码范围: 38-48
• 页数: 11页
• 语种: 英文
• DOI: 10.1093/abbs/gmz136

摘要

Obstructive sleep apnea is characterized by chronic intermittent hypoxia (CIH),which is a risk factor for renal peritubular capillary (PTC) loss,and angiotensin Ⅱ receptor blockers can alleviate PTC loss.However,the mechanism by which losartan (an angiotensin Ⅱ receptor blocker) reduces CIH-induced PTC loss and attenuates kidney damage is still unknown.Thus,in this study,we examined the protective effects of losartan against CIH-induced PTC loss and explored the underlying mechanisms in rat CIH model.The immunohistochemical staining of CD34 and morphological examination showed that CIH reduced PTC density and damaged tubular epithelial cells.Immunohistochemistry,enzyme-linked immunosorbent assay (ELISA),real-time quantitative PCR,and western blot analysis results revealed that CIH increased the expression of hypoxia inducible factor1α(HIF-1α),angiotensin Ⅱ (Ang Ⅱ),angiotensin Ⅱ type 1 receptor (AT1R),pro-angiogenesis factor vascular endothelial growth factor (VEGF),and anti-angiogenesis factor thrombospondin-1 (TSP-1) in the renal cortex of rats.CIH may up-regulate VEGF expression and simultaneously increase TSP-1 production.By histopathological,immunohistochemistry,ELISA,RT-qPCR,and western blot analysis,we found that the expressions of renal renin-angiotensin system (RAS),HIF-1α,VEGF,and TSP-1 were decreased,and PTC loss and tubular epithelial cell injury were attenuated with losartan treatment.Losartan ameliorated CIH-induced PTC loss by modulating renal RAS to improve the crosstalk between endothelial cells and tubular epithelial cells and subsequently regulate the balance of angiogenesis factors.Our study provided novel insights into the mechanisms of CIH-induced kidney damage and indicated that losartan could be a potential therapeutic agent for renal protection by alleviating CIH-induced PTC loss.