Endothelium-derived relaxing factors in the kidney of spontaneously hypertensive rats |
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| Institution: | 1. The Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo 7-3-1 Kongo, Bunkyo-ku, Tokyo 113, Japan;1. Faculty of Pharmaceutical Sciences, University of Tokyo Japan;1. Laboratory for Protein Conformation Diseases, RIKEN Brain Science Institute, Wako, Japan;2. Department of Neurology, Saitama Medical University, Moroyama, Saitama, Japan;3. Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Itabashi-ku, Tokyo, Japan;4. Choju Medical Institute, Fukushimura Hospital, Toyohashi, Japan;5. Department of Medicine for Aging in Place and Community-Based Medical Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan;6. Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD;1. Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Yokohama, Japan;2. Department of Biostatistics, Yokohama City University School of Medicine, Yokohama, Japan;3. Department of Gastroenterology, Chigasaki Municipal Hospital, Chigasaki, Japan;4. Department of Gastroenterology, Yokohama Rosai Hospital, Yokohama, Japan;5. Department of Gastroenterology, Hiratsuka City Hospital, Hiratsuka, Japan;6. Department of Gastroenterology, Kanto Medical Center, NTT East, Shinagawa, Japan;7. Department of Pathology, Yokohama City University, Yokohama, Japan;1. Central Institute for Experimental Animals, Kawasaki, Kanagawa 210-0821, Japan;2. Horizon Discovery, Saint Louis, MO 63146, USA;3. Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, Hiroshima 739-8526, Japan;4. Department of Biosciences and Informatics, Keio University, Yokohama, Kanagawa 223-8522, Japan;5. Department of Oncology, Juntendo University Nerima Hospital, Nerima-ku, Tokyo 177-8521, Japan;6. Medical Proteo Scope Company, Ltd., Yokohama, Kanagawa 236-0004, Japan;7. Department of Molecular Life Science, Division of Basic Medical Science and Molecular Medicine, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan;8. Department of Rheumatology and Clinical Immunology, Clinical Research Center for Rheumatology and Allergy, Sagamihara National Hospital, Sagamihara, Kanagawa 252-0392, Japan;9. Atopy Research Center, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan;10. Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan;11. Advanced Research Center, Keio University, Shinjuku-ku, Tokyo 160-8582, Japan;1. Department of Biological Sciences, Purdue University, West Lafayette, IN 47906, USA;2. Department of Pharmacology, Vanderbilt University, Nashville, TN 37232-0146, USA;3. Department of Biochemistry, Vanderbilt University, Nashville, TN 37232-0146, USA;4. Center for Structural Biology, Vanderbilt University, Nashville, TN 37232-0146, USA;5. Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, TN 37232-0146, USA |
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| Abstract: | Acetylcholine (ACh)-induced vasodilation is mainly due to endothelium-derived nitric oxide (EDNO) and hyperpolarizing factor (EDHF). To explore the mechanisms underlying attenuated endothelium-dependent vasodilation in hypertensive arteries, we measured the EDNO released from isolated kidneys of spontaneously hypertensive rats (SHR) using a sensitive chemiluminescence assay system of NO. ACh-induced renal vasodilation was significantly smaller in SHR than in the normotensive control, Wistar-Kyoto rats (WKY). However, ACh-induced NO release did not differ between SHR and WKY (10−7 M: SHR +37 ± 2 SE] vs. WKY +32 ± 4 fmol/min/g kidney). Perfusion with a 20 mEq/L high-K+ buffer, which is reported to inhibit action of EDHF, significantly reduced ACh-induced vasorelaxation in WKY but not in SHR, resulting in identical renal perfusion pressure in SHR and wKY under these conditions. These results indicate that attenuated ACh-induced vasorelaxation in the SHR kidney may be attributed to a decrease in EDHF rather than that in EDNO. |
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