1995 Fiscal Year Final Research Report Summary
The role of endogenous endothelin (receptor) in injured lung.
| Project/Area Number |
06670605
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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 |
Respiratory organ internal medicine
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| Research Institution | Fukui Medical School |
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Principal Investigator |
ISHIZAKI Takeshi Fukui Med. Sch. School Hospital Faculty of Medicine. Dept of Int. Assistant Professor, 医学部附属病院, 講師 (80151364)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUKAWA Shigeru Fukui Med. Sch. Faculty of Medicine. Ctl. Res. Lab. Associate Professor, 医学部, 助教授 (00092809)
SASAKI Fumihiko Fukui Med. Sch. School Hospital Faculty of Medicine. Dept of Int. Research Assoc, 医学部附属病院, 助手 (70205863)
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| Project Period (FY) |
1994 – 1995
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| Keywords | Isolated perfused lung / Leukotoxuin / Nitric oxide / Vascular endothelial cell / O_2^- / ONOO^- |
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| Research Abstract |
The Summary of our reasearh results are :
In isolated perfused rat lungs leukotoxin (Lx) increased content of endothelin 1 (ET1) in lung tissue and in the perfusate in association with comparable increase in wet lung weight (WLW) and perfusate LDH activity. BQ123, an ET_A receptor antagonist, suppressed such increase of ET1, WLW and perfusate LDH activity. The combinetion of ET1 and Lx, at concentrations that by themselves did not increase WLW,significantly increased WLW as well as the perfusate LDH activity. Pretreatment with BQ123 suppressed the edematous lung injury generated by the combination of ET1 and Lx.
IRL1620, an ET_B receptor agonist, exerted rapid increase in perfusion pressure and edematous lung injury.
In isolated rat pulmonary arterial rings Lx caused endothelin-dependent vasodilation which was significantly suppressed in the presenceof BQ123 or TAK044 (ET nonspecific receptor antagonist) bnt not in the presence of BQ788 (ET_B receptor antagonist) or RES7011 (ET_B receptor antagonist). In human cultured pulmonary endothelial cells Lx enhanced intracellular O_2^- production but either ET1 or ET3 did not show such an effect.
From these experimental results we concluded that Lx, a lung injury producing substance with low dose caused vasodilation and with its higher dose, caused edematous lung injury via activation of ET_A receptor.
We further speculate the possibitity that Lx itselt stimulate ET_A receptor or stimulate the production of ET which act as a messenger.
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