1989 Fiscal Year Final Research Report Summary
The Role of c-AMP and Ca ion on Awake Sheep Lung Injury
| Project/Area Number |
63570347
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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 | Department of Environmental Physiology, Shinshu University School of Medicine |
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Principal Investigator |
UEDA Gou Professor. Department of Environ.Physiol, Shinshu Univ.Sch.Med, 医学部・附属心脈管病研究施設, 教授 (10020702)
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| Co-Investigator(Kenkyū-buntansha) |
KOBAYASHI Michiko Department of Environmental Physiology, 医学部・附属心脈管病研究施設, 助手 (30197280)
HIRAYAMA Jiro First Department of Internal Medicine, 医学部・附属病院第1内科, 助手 (90156696)
KUBO Keishi First Department of Internal Medicine, 医学部・附属病院第1内科, 講師 (80143965)
SAKAI Akio Department of Environmental Physiology, 医学部・附属心脈管病研究施設, 助教授 (70020758)
KOBAYASHI Toshio First Department of Internal Medicine, 医学部・附属病院第1内科, 講師 (80020775)
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| Project Period (FY) |
1988 – 1989
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| Keywords | Eudotoxin / db c-AMP / Pulmonary circulation / lung lymph / laser-Doppler method |
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| Research Abstract |
(1) Sheep lung injury was produced by hypobaric hypoxia which caused hypoxic pulmonary vasoconstriction. This was inhibited by administration of dibutyryl c-AMP. The effect was proved either in the case of the administration 20min before hypobaric exposure or 20 min after the exposure. For the systemic blood pressure, db c-AMP did not cause any significant change. The inhibitory effect of db c-AMP for endotoxin-induced lung injury was also known tobe remarkable. In another series of experiments our group members tested the pretreatment-inhibition potential of chlorpheniramine ( an HI receptor antagonist), db c-AMP, and the Ca channel antagonists verapamil and nifedipine on polybrene-induced lung injury. It was thus found that only verapamil and db c-AMP significantly attenuated the permeability effects of polybrene.It was interpreted that the permeability alteration induced by polybrene could be modulated by intracellular calcium and/or c- AMP levels.
(2) The effects of the cell-permeab
… More
le dibutyryl derivative of c- AMP on the vascular reactivity of isolated perfused rat lungs were examined. In lungs perfused with homologous blood, pulmonary arterial infusion of db c-AMP (30 micro g/min) inhibited hypoxia- induced vasoconstriction and vasoconstriction due to bolus injection of angiotensin II. Cyclic AMP phosphodiesterase inhibition by aminophylline acted synergistically with db c-AMP in the reduction of hypoxia-induced vasoconstriction. In lungs perfused with cell and protein-free salt solution, db cAMP inhibited both initial and prolonged vasoconstriction following bolus injection of 2 micro g leukotriene C4. It is therefor considered that db c-AMP inhibited pulmonary vascular reactivity nonspecifically.
(3) Using rabbit earlobes immersed in cold liquid, capillary blood flow was compensated by opening of arterio-venous anastomoses. This phenomenon was noticed from the pattern change of the record obtained by a laser-Doppler tissue flow meter.
(4) These animal experiments were in some cases being tested in human high altitude responses and the treatment is being tested. Less
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