1997 Fiscal Year Final Research Report Summary
Development of sensitve assay of NO and its clinical application
Project/Area Number |
07557055
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Research Category |
Grant-in-Aid for Scientific Research (A)
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Allocation Type | Single-year Grants |
Section | 展開研究 |
Research Field |
Circulatory organs internal medicine
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Research Institution | University of Tokyo |
Principal Investigator |
HIRATA Yasunobu Univ.of Tokyo, Medicine, Associate Prof., 医学付属病院, 講師 (70167609)
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Co-Investigator(Kenkyū-buntansha) |
GYOUTOKU Yuichi Ajinomoto Co., Central Research Institute, Chief, 所長
MABUCHI Kunihiko Univ.of Tokyo, Research Center for Advanced Science and Technology, Prof., 先端科学技術センター, 教授 (50192349)
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Project Period (FY) |
1995 – 1997
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Keywords | nitric oxide / chemiluminescence / inhalation / exhaled air / arteriosclerosis / kidney |
Research Abstract |
The aims of the present study were development of highly sensitive NO assay system and its clinical application. We newly developed luminol chemiluminescence assay for NO and applied it to the rat isolated perfused kidney. Using this system, we found that endothelin-1 released NO through stimulation of ETB receptors and that this response was attenuated in the vessels with endothelial damage. Adrenomedullin, of which second messenger had been believed only cAMP,exhibited vasodilatory action by NO-cGMP system. Vasopressin increased NO release through V1 receptors. In particular, in arteriosclerotic vessels, NO may greatly influence a role of these vasoactive substances in regulation of vascular tone. We analyzed NO output in the exhaled air of patients with liver cirrhosis and renal failure by ozone chemiluminescence, and found the increase in NO excretion. Furthermore, we developed a fluorescein specifically sensitive to NO,and succeeded in bioimaging analysis of NO in the cultured cells and tissue slices. We also tried an NO inhalation therapy in patients with heart failure. Inhaled NO dilated pulmonary vessels without changes in systemic vasculature, resulting in an increase in gas exchange. Moreover, NO gas improved exercise capacity in these patients. These results suggest that NO inhalation may be useful for improvement of quality of life in heart failure.
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[Publications] Hirata Y,Hayakawa H,Kakoki M,Tojo A,Suzuki E,Nagata D,Kimura K,Goto A,Kikuchi K,Nagano T,Hirobe M,Omata M.: "Receptor subtype for vasopressin-induced release of nitric oxide from rat kidney." Hypertension. 29. 58-64 (1997)
Description
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