Differences in the Metabolism of 18:2n-6 and 18:3n-6 by the Liver and Kidney May Explain the Antihypertensive Effect of 18:3n-6 |
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| Affiliation: | 1. Department of Entomology and MOA Key Laboratory for Monitoring and Environment-Friendly Control of Crop Pests, College of Plant Protection, China Agricultural University, Beijing 100193, China;1. Department of Biochemistry and Immunology, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil;2. Department of Pharmacology, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil;3. Department of Cellular and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil;4. Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, São Paulo, Brazil;5. Division of Nephrology, School of Medicine, Federal University of São Paulo, São Paulo, Brazil;6. Fiocruz-Bi-Institutional Translational Medicine Project, University of São Paulo, Ribeirão Preto, São Paulo, Brazil;7. Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany;8. Institute of Systems Immunology, Center for Tumor and Immunology, University of Marburg, Marburg, Germany;1. Division of Virology, Institute of Medical Science, University of Tokyo, Tokyo, Japan;2. The Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute, Tokyo, Japan;3. Department of Infectious Diseases and Applied Immunology, IMSUT Hospital of The Institute of Medical Science, University of Tokyo, Tokyo, Japan;4. Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan;5. National Institute of Infectious Diseases, Tokyo, Japan;6. Clinic of Nihon Sumo Kyokai, Tokyo, Japan;7. Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA;8. The University of Tokyo, Pandemic Preparedness, Infection and Advanced Research Center (UTOPIA), Tokyo, Japan |
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| Abstract: | The present study examined the in vitro and in vivo metabolism of 18:2n-6 and 18:3n 6 by kidney and liver in the male adult spontaneously hypertensive (SHR) and normotensive (WKY) rats. In liver and kidney slices incubated for 1 h with either [1-14C]18:2n-6 or [1-14C]18:3n-6 (60 μM), substantial amounts of radioactivity were incorporated into triacylglycerol and phospholipid fractions. Approximately 15% of the radiolabeled 18:2n-6 was converted into 18:3n-6 in liver slices but no conversion was found in kidney slices. When incubated with radiolabeled 18:3n-6, over 40% of the radioactivity was metabolized mainly to 20:4n-6 in liver slices, but evenly to 20:3n-6 and 20:4n-6 in kidney slices. There were no differences between the results from SHR and those from WKY. In WKY rats given an oral bolus of radiolabeled 18:3n-6, most of the radioactivity was recovered in the liver and significantly less in the kidney. In both tissues, the radioactivity was associated initially only with 18:3n-6 and later with its elongation product, 20:3n-6. These findings indicated that the kidney, although unable to metabolize 18:2n-6, could metabolize 18:3n-6 taken up from the circulation. The effectiveness of 18:3n-6, compared to 18:2n-6, as an anti hypertensive agent may result from the provision of a post-Δ6-desaturation metabolite which can be directly converted to blood pressure-regulating eicosanoids in the kidney. |
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