Early antihypertensive treatment and ischemia-induced acute kidney injury

Item Type:	Article
Title:	Early antihypertensive treatment and ischemia-induced acute kidney injury
Creators Name:	Greite, R. and Derlin, K. and Hensen, B. and Thorenz, A. and Rong, S. and Chen, R. and Hellms, S. and Jang, M.S. and Bräsen, J.H. and Meier, M. and Willenberg, I. and Immenschuh, S. and Haller, H. and Luft, F.C. and Panigrahy, D. and Hwang, S.H. and Hammock, B.D. and Schebb, N.H. and Gueler, F.
Abstract:	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.
Keywords:	Acute Kidney Injury, Chronic Kidney Disease, Hypertension, Renal Perfusion, Soluble Epoxide Hydrolase Inhibitor, Animals, Mice
Source:	American Journal of Physiology Renal Physiology
ISSN:	1931-857X
Publisher:	American Physiological Society
Volume:	319
Number:	4
Page Range:	F563-F570
Date:	October 2020
Additional Information:	Copyright © 2020 the American Physiological Society
Official Publication:	https://doi.org/10.1152/ajprenal.00078.2020
External Fulltext:	View full text on PubMed Central
PubMed:	View item in PubMed

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