Brown A J, Nally J E
School of Biological and Biomedical Sciences, Glasgow Caledonian University, 70 Cowcaddens Road, Glasgow G4 0BA, Scotland, UK.
Clin Sci (Lond). 2001 Jan;100(1):19-23.
Angiotensin II potentiates methacholine-evoked bronchoconstriction both in bovine airways in vitro and in asthmatic patients in vivo. Angiotensin II also potentiates endothelin-1-evoked contractions in vitro, but fails to alter such contractions in vivo. One possible confounding factor in patients is their use of inhaled corticosteroids. Accordingly the present study examined the effects of hydrocortisone (cortisol) on contractions evoked by methacholine and endothelin-1 in the presence and absence of angiotensin II. Contractions of rings of isolated bovine airways were measured isometrically in organ baths. Concentration-response curves were obtained for endothelin-1 or methacholine in the presence and absence of angiotensin II, hydrocortisone and a combination of angiotensin II and hydrocortisone. Hydrocortisone abolished the angiotensin II-mediated potentiation of endothelin-1-evoked, but not methacholine-evoked, contractions. Hydrocortisone alone evoked the enhancement of methacholine responses, similar to the effect produced by angiotensin II. While species differences may exist, our present results suggest that the use of corticosteroids can have a profound effect on the interaction between angiotensin II and endothelin-1. Accordingly, the presence of inhaled corticosteroids might explain the differences between the results obtained in vitro and in vivo.
血管紧张素II在体外牛气道和体内哮喘患者中均可增强乙酰甲胆碱诱发的支气管收缩。血管紧张素II在体外也可增强内皮素-1诱发的收缩，但在体内却不能改变这种收缩。患者中一个可能的混杂因素是他们使用吸入性皮质类固醇。因此，本研究在有和没有血管紧张素II的情况下，检测了氢化可的松（皮质醇）对乙酰甲胆碱和内皮素-1诱发的收缩的影响。在器官浴槽中以等长方式测量离体牛气道环的收缩。在有和没有血管紧张素II、氢化可的松以及血管紧张素II与氢化可的松组合的情况下，获得内皮素-1或乙酰甲胆碱的浓度-反应曲线。氢化可的松消除了血管紧张素II介导的对内皮素-1诱发的而非乙酰甲胆碱诱发的收缩的增强作用。单独使用氢化可的松可诱发乙酰甲胆碱反应增强，类似于血管紧张素II产生的效应。虽然可能存在种属差异，但我们目前的结果表明，皮质类固醇的使用可能对血管紧张素II和内皮素-1之间的相互作用产生深远影响。因此，吸入性皮质类固醇的存在可能解释了体外和体内所得结果之间的差异。
