Hypoxia/reoxygenation enhances murine afferent arteriolar vasoconstriction by angiotensin II.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY(2018)
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. Hematoxylin and eosin staining was used to estimate slice viability. Arterioles in the slices were located by differential interference contrast microscopy, and responses to vasoactive substances were assessed. Cytosolic calcium transients and NADPH oxidase (NOX) 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 reoxygenation (H/R). H/R resulted in enhanced necrotic tissue damage compared with control conditions. To characterize the slice model, we applied ANG II (10(-7) M), norepinephrine (NE; 10(-5) M), endothelin-1 (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%, respectively. H/R significantly increased the ANG II response compared with 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.
MoreTranslated text
Key words
acute kidney injury,afferent arterioles,angiotensin II,hypoxia-reoxygenation,live kidney slices,vasoconstriction
AI Read Science
Must-Reading Tree
Example
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
Generate MRT to find the research sequence of this paper
Chat Paper
Summary is being generated by the instructions you defined