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Hypoxia-reoxygenation enhances murine afferent arteriolar vasoconstriction by angiotensin II

Item Type:Article
Title:Hypoxia-reoxygenation enhances murine afferent arteriolar vasoconstriction by angiotensin II
Creators Name:Pahlitzsch, T.M. and Liu, Z.Z. and Al-Masri, A. and Braun, D. and Dietze, S. and Persson, P.B. and Schunck, W.H. and Blum, M. and Kupsch, E. and Ludwig, M. and Patzak, A.
Abstract:We tested the hypothesis that hypoxia/reoxygenation (H/R) augments vasoreactivity to angiotensin II (Ang II). In particular, we compared an in situ live kidney slice model with isolated afferent arterioles (C57Bl6 mice) to assess the impact of tubules on microvessel response. H&E staining was used to estimate slice viability. Arterioles in the slices were located by DIC microscopy, and responses to vasoactive substances were assessed. Cytosolic calcium transients and NADPH oxidase mRNA expression were studied in isolated afferent arterioles. SOD activity was measured in live slices. Both experimental models were subjected to control and H/R treatment (60 min). Slices were further analyzed after 30, 60 and 90 min hypoxia followed by 10 or 20 min re-oxygenation. H/R resulted in enhanced necrotic tissue damage compared to control conditions. To characterize the slice model, we applied Ang II (10-7 M), NE (10-5 M), ET-1 (10-7 M) and ATP (10-4 M) reducing the initial diameter to 44.5+/-2.8%, 50.0+/-2.2%, 45.3+/-2.6%, and 74.1+/-1.8%. H/R significantly increased the Ang II response compared to control in live slices and in isolated afferent arterioles, although calcium transients remained similar. Tempol incubation prevented the H/R effect on Ang II responses. H/R significantly increased NOX2 mRNA expression in isolated arterioles. SOD activity was significantly decreased after H/R. Enhanced arteriolar responses after H/R occurred independently from the surrounding tissue indicating no influence of tubules on vascular function in this model. The mechanism of increased Ang II response after H/R might be increased oxidative stress and increased calcium sensitivity of the contractile apparatus.
Keywords:Acute Kidney Injury, Afferent Arterioles, Angiotensin II, Hypoxia-Reoxygenation, Live Kidney Slices, Vasoconstriction, Animals, Mice
Source:American Journal of Physiology Renal Physiology
ISSN:1931-857X
Publisher:American Physiological Society (U.S.A.)
Volume:314
Number:3
Page Range:F430-F438
Date:March 2018
Official Publication:https://doi.org/10.1152/ajprenal.00252.2017
PubMed:View item in PubMed

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