Project/Area Number |
06404027
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Research Category |
Grant-in-Aid for General Scientific Research (A)
|
Allocation Type | Single-year Grants |
Research Field |
Hygiene
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Research Institution | University of Tokyo |
Principal Investigator |
WADA Osamu Department of Hygiene and preventive Medicine, University of Tokyo, Professor, 医学部(医), 教授 (60009933)
|
Co-Investigator(Kenkyū-buntansha) |
YANAGISAWA Hiroyuki Department of Hygiene and preventive Medicine, Saitama Medical School, Associate, 医学部, 助教授 (10200536)
YAMAZAKI Nobuyuki Department of Hygiene and preventive Medicine, University of Tokyo, Research Ass, 医学部(医), 教務職員 (40143424)
NAGAHASHI Masaru Department of Hygiene and preventive Medicine, University of Tokyo, Assistant Pr, 医学部(医), 助手 (90009994)
|
Project Period (FY) |
1994 – 1995
|
Project Status |
Completed (Fiscal Year 1995)
|
Budget Amount *help |
¥35,700,000 (Direct Cost: ¥35,700,000)
Fiscal Year 1995: ¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 1994: ¥21,300,000 (Direct Cost: ¥21,300,000)
|
Keywords | Kidney / EFAD / Eicosanoid / Cyclooxggenase / サイクロオキシゲナーゼ |
Research Abstract |
Essential fatty acid defficiency (EFAD) ameliorates the decrease in GFR and renal plasma flow that occurs 24 hours after the onset of bilateral ureteral obstruction (BUO). The vasoactive hormones, prostaglandins (PGs) and thromboxane (Tx), have a role in the changes in renal function described above. Thus, we evaluated the effect of essential fatty acid defficiency on the prodnction of PGE_2,6-keto PGF_1 alpha and TxB_2 and the activities of PGE_2 isomerase, PGI_2 synthase, Tx synthase and cyslooxygenase (COX) in glomeruli isolated from sham-operated control (SOC) and BUO rats fed an EFAD diet or a standard diet for approximately 4 weeks. A standarded diet significantly increased the glomerular production of PGE_2,6-keto PGF_1 alpha and TxB_2 in BUO vs SOC rats. The production rates of eicosanoids correlated well with the activities of PGE_2 isomerase, PGI_2 synthase, Tx synthase and COX.On the other hand, an essential fathy acid defficiency aboloshed the increase in glomerular eicosanoid production seen in rats with BUO.The synthetic levels of eicosanoids were comparable in SOC and BUO rats fed an EFAD diet, indicating normalization of glomerular eicosanoid production duo to EFAD.Moreover, there were no significant differences in the activities of PGE_2 isomerase, PGI_2 synthase, Tx synthase and COX between the SOC and BUO rats. Thus, our results indicate that EFAD prevents the increase in production of eicosanoids by glomeruli due to inactivation of COX and eicosanoid-forming synthases in the setting of BUO of 24 hours duration. The protective effect of EFAD on renal function in rats with BUO may be due in part to normalization of the glomerular production of eicosanoids, particularly TxA_2.
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