Rationale - Acute kidney injury (AKI) frequently complicates major surgery and can be associated with hypertension and progress to chronic kidney disease (CKD), but reports on blood pressure normalization in AKI are conflicting. Objective - We investigated the effects of the angiotensin converting enzyme (ACE) inhibitor, enalapril, and the soluble epoxide hydrolase inhibitor (sEHI), 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), on renal inflammation, fibrosis and glomerulosclerosis in a mouse model of ischemia-reperfusion-induced (IRI) AKI. Methods and Results - Male CD1 mice underwent unilateral IRI for 35 min. Blood pressure was measured by tail cuff and mesangial matrix expansion was quantified on methenamine silver stained sections. Renal perfusion was assessed by functional magnetic resonance imaging (MRI) in vehicle and TPPU treated mice and histology and immunohistochemistry was done to study severity of AKI and inflammation. Leukocyte subsets were analyzed by flow cytometry and pro-inflammatory cytokines by qPCR. Plasma and tissue levels of TPPU and lipid mediators were analyzed by liquid chromatography mass spectrometry. IRI resulted in 20 mm Hg blood-pressure increase in the vehicle group. TPPU and enalapril normalized blood pressure and reduced mesangial matrix expansion. However, inflammation and progressive renal fibrosis were severe in all groups. TPPU further reduced renal perfusion on day 1 and 14. Conclusions - Early antihypertensive treatment worsened renal outcome after AKI by further reducing renal perfusion despite reduced glomerulosclerosis.

中文翻译：

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早期抗高血压治疗和缺血引起的急性肾损伤。

基本原理 - 急性肾损伤 (AKI) 经常使大手术复杂化，并且可能与高血压和慢性肾病 (CKD) 的进展有关，但关于 AKI 血压正常化的报道相互矛盾。目的 - 我们研究了血管紧张素转化酶 (ACE) 抑制剂依那普利和可溶性环氧化物水解酶抑制剂 (sEHI) 1-三氟甲氧基苯基-3-(1-丙酰哌啶-4-基) 脲 (TPPU) 对肾功能的影响。缺血再灌注诱导 (IRI) AKI 小鼠模型中的炎症、纤维化和肾小球硬化。方法和结果 - 雄性 CD1 小鼠接受单侧 IRI 35 分钟。通过尾套测量血压，并在甲基苯胺银染色切片上量化系膜基质膨胀。在载体和 TPPU 治疗的小鼠中通过功能磁共振成像 (MRI) 评估肾灌注，并进行组织学和免疫组织化学以研究 AKI 和炎症的严重程度。通过流式细胞术分析白细胞亚群，通过 qPCR 分析促炎细胞因子。TPPU 和脂质介质的血浆和组织水平通过液相色谱质谱法进行分析。IRI 导致赋形剂组血压升高 20 mmHg。TPPU 和依那普利使血压正常化并减少系膜基质扩张。然而，所有组的炎症和进行性肾纤维化都很严重。TPPU 在第 1 天和第 14 天进一步降低肾灌注。 结论 - 尽管肾小球硬化减少，但早期抗高血压治疗通过进一步降低肾灌注使 AKI 后的肾脏结果恶化。