Renal cytochrome P-450-dependent metabolism of arachidonic acid in spontaneously hypertensive rats
Biochemical Pharmacology, ISSN: 0006-2952, Vol: 37, Issue: 3, Page: 521-527
1988
- 82Citations
- 6Captures
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Metrics Details
- Citations82
- Citation Indexes82
- 82
- CrossRef61
- Captures6
- Readers6
Article Description
Renal cytochrome P-450-dependent monooxygenases metabolize arachidonic acid to products some of which affect vascular tone and (Na +, K + )ATPase activity. We measured these metabolites in spontaneously hypertensive (SHR) and control normotensive Wister-Kyoto (WKY) rats. Systolic tail blood pressure in SHR increased from 112 to 202 mm Hg and in WKY from 97 to 136 mm Hg at 5 and 20 weeks respectively. Renal cortical and outer medullary microsomes were incubated with [ 14 C]arachidonic acid; metabolites formed via the cytochrome P-450 pathway were defined as those dependent on NADPH, inhibited by SKF-525A, and unaffected by indomethacin. The P-450-dependent metabolites were higher in SHR vs WKY at 5, 7 and 11 weeks in the cortex and at 7 and 11 weeks in the outer medulla. In the outer medulla, the formation of these metabolites peaked at 7 weeks. Using reverse-phase HPLC, the cytochrome P-450-dependent metabolites were separated into three radioactive peaks: peak I had a retention time of 17.5 min and comigrated as 11,12-dihydroxyeicosatrienoic acid standard. Peak II had a retention time of 19 min and comigrated with ω-hydroxylation compounds. Peak III had a retention time of 27 min and comigrated with 11,12-epoxyeicosatrienoic acid. In the renal cortex, peak I was higher in SHR vs WKY at 5, 7, and 9 weeks and peak III at 5, 7, 9 and 11 weeks. In the outer medulla, peak I was higher in SHR at 5 and 7 weeks, and peaks II and III at 7 weeks. Cytochrome P-450 content in the renal cortex was always higher in SHR vs WKY. We conclude that renal cytochrome P-450-dependent metabolites of arachidonic acid may participate in the circulatory changes of SHR, particularly during the developmental stage.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/0006295288902237; http://dx.doi.org/10.1016/0006-2952(88)90223-7; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=0023839318&origin=inward; http://www.ncbi.nlm.nih.gov/pubmed/3122763; https://linkinghub.elsevier.com/retrieve/pii/0006295288902237; http://dx.doi.org/10.1016/0006-2952%2888%2990223-7; https://dx.doi.org/10.1016/0006-2952%2888%2990223-7
Elsevier BV
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