Open AccessEarly antihypertensive treatment and ischemia-induced acute kidney injury
Author(s) -
Robert Greite,
Katja Derlin,
Bennet Hensen,
Anja Thorenz,
Song Rong,
Rongjun Chen,
Susanne Hellms,
Mi-Sun Jang,
Jan Hinrich Bräsen,
Martin Meier,
Ina Willenberg,
Stephan Immenschuh,
Hermann Haller,
Friedrich C. Luft,
Dipak Panigrahy,
Sung Hee Hwang,
Bruce D. Hammock,
Nils Helge Schebb,
Faikah Gueler
Publication year - 2020
Publication title -
american journal of physiology. renal physiology./american journal of physiology. renal physiology
Language(s) - English
Resource type - Journals
eISSN - 1931-857X
pISSN - 1522-1466
DOI - 10.1152/ajprenal.00078.2020
Subject(s) - medicine , urology , glomerulosclerosis , blood pressure , acute kidney injury , creatinine , fibrosis , proinflammatory cytokine , kidney , pathology , inflammation , proteinuria
Acute kidney injury (AKI) frequently complicates major surgery and can be associated with hypertension and progress to chronic kidney disease, but reports on blood pressure normalization in AKI are conflicting. In the present study, we investigated the effects of an angiotensin-converting enzyme inhibitor, enalapril, and a soluble epoxide hydrolase inhibitor, 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl)urea (TPPU), on renal inflammation, fibrosis, and glomerulosclerosis in a mouse model of ischemia-reperfusion injury (IRI)-induced AKI. 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 MRI in vehicle- and TPPU-treated mice. Immunohistochemistry was performed to study the severity of AKI and inflammation. Leukocyte subsets were analyzed by flow cytometry, and proinflammatory cytokines were analyzed by quantitative PCR. Plasma and tissue levels of TPPU and lipid mediators were analyzed by liquid chromatography mass spectrometry. IRI resulted in a blood pressure increase of 20 mmHg in the vehicle-treated 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 days 1 and 14 . In conclusion, early antihypertensive treatment worsened renal outcome after AKI by further reducing renal perfusion despite reduced glomerulosclerosis.