| Project/Area Number |
11671481
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | Tokyo University |
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Principal Investigator |
ORII Ryo The university of Tokyo Hospital, Department of Anesthesiology, Assistant Professor, 医学部・付属病院, 助手 (30272579)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Hirotoshi The university of Tokyo Hospital, Department of Anesthesiology, Assistant Professor, 医学部・付属病院, 助手 (30292931)
YAMADA Yoshitsugu The university of Tokyo branch hospital, Department of Anesthesiology, Associate Professor, 医学部・付属病院分院, 助教授 (30166748)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2000: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1999: ¥3,300,000 (Direct Cost: ¥3,300,000)
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| Keywords | acctylcholine / muscarinic receptor / pulmonary circulation |
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| Research Abstract |
Limited information about the muscarinic receptor subtype (s) mediating pulmonary circulatory vasodilator responses to acetylcholine (ACh) is available. The aim of this study was to characterize pharmacologically the muscarinic receptors associated with ACh-induced pulmonary vasodilation. Vasodilation of rabbit isolated buffer-perfused lungs in which pulmonary hypertension had been induced with the thromboxane A_2 analogue U-46619 was evoked by ACh, at a just maximally effective concentration (2×10^<-7> M). The effects of cumulative concentrations of three specific muscarinic receptor subtype antagonists [pirenzepine (M_1), methoctramine (M_2) and 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, M_3)] on ACh-induced pulmonary vasodilation were determined. The double vascular occlusion pressure was recorded to localize the muscarinic receptors within the pulmonary vasculature. According to their 50% inhibitory concentrations (IC_<50>s), the rank of order of antagonist potency was 4-DAMP >> pirenzepine>methoctramine. The vascular effects of all three inhibitors were localized to the precapillary segment. These data suggest that the vasodilator action of ACh on rabbit isolated perfused U-46619-pretreated lungs is mediated solely by M_3 muscarinic receptors localized in the pulmonary arterial bed.
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