Substance P-induced bronchoconstriction in the guinea pig. Enhancement by inhibitors of neutral metalloendopeptidase and angiotensin-converting enzyme.
Substance P-induced bronchoconstriction in the guinea pig. Enhancement by inhibitors of neutral metalloendopeptidase and angiotensin-converting enzyme.
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P 物质诱导豚鼠支气管收缩。
DOI：
10.1164/ajrccm/137.2.331
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Drazen,JM
中科院分区：
文献类型：
--
作者：
Shore,SA;Stimler-Gerard,NP;Coats,SR;Drazen,JM
我们测试了中性金属内肽酶（NEP）抑制剂thiorphan（0.17、0.5和1.7 mg i. v.）和血管紧张素转换酶（ACE）抑制剂captopril（0.5、1.7和5.0 mg i. v.）对麻醉机械通气豚鼠快速静脉输注P物质（0.1 - 30 nmol/kg）的支气管收缩反应的影响。在接受硫啡烷或巯甲丙脯酸治疗的动物中，P物质引起的肺电导和动态顺应性的降低比对照动物更大。Thiorphan（0.5 mg）对静脉注射乙酰甲胆碱的气道反应性没有影响，而Captopril（1.7 mg）引起乙酰甲胆碱反应性的小幅增加。这两种药物显着增加了回收的免疫反应性物质P在动脉血浆外源性给药后的肽。我们的结论是，P物质的降解NEP和ACE是重要的，以确定由静脉注射这种神经肽引起的支气管收缩的幅度。这些数据表明，与肽酶活性降低相关的条件可能导致对引起内源性P物质释放的刺激的反应增强。
We tested the effects of the neutral metalloendopeptidase (NEP) inhibitor, thiorphan (0.17, 0.5, and 1.7 mg i.v), and the angiotensin-converting enzyme (ACE) inhibitor, captopril (0.5, 1.7, and 5.0 mg i.v.), on the bronchoconstrictor response to rapid intravenous infusions of substance P (0.1 to 30 nmol/kg) in anesthetized, mechanically ventilated guinea pigs. The decreases in pulmonary conductance and dynamic compliance caused by substance P were greater in animals treated with either thiorphan or captopril than in control animals. Thiorphan (0.5 mg) had no effect on airway responsiveness to intravenously administered methacholine, whereas captopril (1.7 mg) caused a small increase in methacholine responsiveness. Both drugs significantly increased the recovery of immunoreactive substance P in arterial plasma after exogenous administration of the peptide. We conclude that degradation of substance P by both NEP and ACE is important for determining the magnitude of the bronchoconstriction caused by intravenous administration of this neuropeptide. These data suggest that conditions associated with diminished peptidase activity could result in enhanced responses to stimuli which cause the release of endogenous substance P.