| Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1994: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1993: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1992: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Research Abstract |
Bronchopulmonary neuroepithelial bodies (NEBs), composed of inervated clusters of amine-and peptide-containg cells, are widely distributed thoughout the airway mucosa of human and animal lungs. Structurally, NEBs resemble chemoreceptors such as corotid bodies, taste buds and are thought to function as hypoxia sensitive airway sensors. Using histchemical and histimmunochemical techniques, NEBs have been shown to contain serotonine (5-HT) and peptidelike substances in their cytoplasmic vesicles. Undre alveolar hypoxia, NEBs have been shown to release the vesicles to intercellular space. Though the mechanism of oxygen sensing by these cells and the physiological roles of the release are unknown, we hypothesize that the release of vesicles which contain 5-HT play essential roles in the responses of pulmonary vascular constriction to inhalational hypoxia (hypoxic pulmonary vasoconstriction(HPV). In this study, we used isolated lung perfusion models of rats and investigated the effects of 5-HT antagonist, ketanserin, and inhalational anesthetics, sevoflurane, isoflurane on the responses of NEBs to hypoxia and HPV.
Administration of ketanserin to the perfusate completely inhibited the response of pulmonary vascluar constriction to inhalational hypoxis. The inhibition of HPV was not recovered after washout of ketanserin from the perfusate. These findings strongly suggest that the mediator which causes HPV is 5-HT and that ketanserin binds to the receptor irreversibly.
Both inhalational anesthetics sevoflurane and isoflurane inhibited HPV dose dependedly. Inhalational concentrations of 4% sevoflurane and 3% isoflurane completely blocked the response. But the responses of pulmonary vessels to hypoxia was recovered at 60 min after cessation of inhalation. The inhibitory effects of the anesthetics on HPV were reversible.
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