1988 Fiscal Year Final Research Report Summary
Studies on the Regulatory Mechanism of Renal Erythropoietin Production.
| Project/Area Number |
61570050
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
General physiology
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| Research Institution | Nara Medical University |
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Principal Investigator |
ENOKI Yasunori Professor, Department of Physiology, Nara Medical University, 医学部, 教授 (00075029)
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| Co-Investigator(Kenkyū-buntansha) |
OHGA Yoshimi Research Associate, Department of Physiology, Nara Medical Univ., 医学部, 助手 (70094539)
SAKATA Susumu Research Associate, Department of Physiology, Nara Medical Univ., 医学部, 助手 (20142383)
KOHZUKI Hisaharu Assistant Professor, Department of Physiology, Nara Medical Univ., 医学部, 講師 (20175326)
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| Project Period (FY) |
1986 – 1988
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| Keywords | Erythropoietin / Hypoxia / Blood Oxygen Affinity / Plasma / Erythriod Colony Inhibitor(s) / コロニー形成阻害因子 |
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| Research Abstract |
A versatile hypobaric chamber was designed, home-made, and used for exposing mice to hypobaric hypoxia, and a rapid microtonometric system was developed for point to point determination of oxygen dissociation curve of less than 1 ml blood. Since an erythroid colony inhibitor(s) was found in murine plasma, we attempted to find an effective procedure to eliminate the inhibitor(s) therefrom. After scrutinization of 13 pretreatment methods, the procedure of chloroform shaking followed by dialysis was concluded to be the best. When normal mice (P<@D25@>Dd2: 40.4 2.2 Torr) were exposed to hypobaric hypoxia of 350 Torr for up to 10 days, the Epo level started to elevate after a few hours, reaching peak values at the 2nd. to 3rd. day, and afterwards declined gradually. The epo level at the peak was elevated four-fold as compared with the prehypoxic value. Mice with blood of higher oxygen affinity (P<@D25@>Dd2: 30.1 1.5 Torr), which was induced by oral administration of 0.5 % sodium cyanate, showed a little or no elevation of the Epo level when exposed to the same hypobaric hypoxia. Under more advanced hypoxia of 200 Torr, both normal and cyanated mice exhibited a similar and remarkable extent of the epo Response. The elevation at the peak was five-fold over the prehypoxic level. These results imply that the (renal) tissues relevant to either Epo production or oxygen sensing or both is less hypoxic under 350 Torr in cyanated mice with higher oxygen affinity of blood than in normal mice, and that the physiologically optimal oxygen affinity of blood is variable depending upon severity of hypoxia. The plasma erythroid colony inhibitor(s) showed an inverse temporal change to that of Epo, which suggested a possible important role of this factor in regulation of erythropoiesis under hypoxic conditions.
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