Kanazawa H, Kawaguchi T, Fujii T, Shoji S, Hirata K, Kudoh S, Kurihara N, Yoshikawa J
First Department of Internal Medicine, Osaka City University Medical School, Japan.
Thorax. 1996 Dec;51(12):1199-202. doi: 10.1136/thx.51.12.1199.
Adrenomedullin is a hypotensive peptide recently discovered in human phaeochromocytoma which has been found to inhibit bronchoconstriction induced by histamine and acetylcholine. This study was designed to determine the manner in which adrenomedullin and other bronchodilators interact in modulating airway function.
A study was undertaken to determine whether adrenomedullin potentiated the bronchoprotective effects of isoprenaline, vasoactive intestinal peptide (VIP), and theophylline against histamine-induced bronchoconstriction in anaesthetised guinea pigs in vivo.
Adrenomedullin in a concentration of 10(-9) M significantly inhibited histamine-induced bronchoconstriction but in a concentration of 10(-10) M it did not exhibit the bronchoprotective effect against histamine. VIP (10(-9) M) did not affect histamine-induced bronchoconstriction but it markedly inhibited the bronchoprotective effect against histamine in the presence of adrenomedullin (10(-10) M). VIP (10(-6) M) significantly inhibited histamine-induced bronchoconstriction but this effect was short lived. Adrenomedullin in a concentration of 10(-10) M potentiated bronchoprotection induced by VIP (10(-6) M) and prolonged it. Isoprenaline (10(-8) M) also significantly inhibited histamine-induced bronchoconstriction and this effect was enhanced in the presence of adrenomedullin (10(-10) M). Similarly, adrenomedullin (10(-10) M) significantly potentiated theophylline-induced bronchoprotection, and a sub-bronchoprotective dose of theophylline (20 mg/kg i.p.) was effective in preventing histamine-induced bronchoconstriction in the presence of adrenomedullin (10(-10) M).
This study shows that adrenomedullin potentiates the bronchoprotective effects of different classes of bronchodilators against histamine challenge in anaesthetised guinea pigs.
肾上腺髓质素是最近在人嗜铬细胞瘤中发现的一种降压肽，已发现它能抑制组胺和乙酰胆碱诱导的支气管收缩。本研究旨在确定肾上腺髓质素与其他支气管扩张剂在调节气道功能中相互作用的方式。
进行了一项研究，以确定在体内麻醉的豚鼠中，肾上腺髓质素是否能增强异丙肾上腺素、血管活性肠肽（VIP）和茶碱对组胺诱导的支气管收缩的支气管保护作用。
浓度为10⁻⁹ M的肾上腺髓质素能显著抑制组胺诱导的支气管收缩，但浓度为10⁻¹⁰ M时对组胺没有支气管保护作用。VIP（10⁻⁹ M）不影响组胺诱导的支气管收缩，但在存在肾上腺髓质素（10⁻¹⁰ M）的情况下，它能显著抑制对组胺的支气管保护作用。VIP（10⁻⁶ M）能显著抑制组胺诱导的支气管收缩，但这种作用持续时间较短。浓度为10⁻¹⁰ M的肾上腺髓质素能增强VIP（10⁻⁶ M）诱导的支气管保护作用并延长其作用时间。异丙肾上腺素（10⁻⁸ M）也能显著抑制组胺诱导的支气管收缩，在存在肾上腺髓质素（10⁻¹⁰ M）的情况下，这种作用增强。同样，肾上腺髓质素（10⁻¹⁰ M）能显著增强茶碱诱导的支气管保护作用，并且在存在肾上腺髓质素（10⁻¹⁰ M）的情况下，低于支气管保护剂量的茶碱（20 mg/kg腹腔注射）能有效预防组胺诱导的支气管收缩。
本研究表明，在麻醉的豚鼠中，肾上腺髓质素能增强不同类别的支气管扩张剂对组胺激发的支气管保护作用。
