Tokuyama K, Lötvall J O, Löfdahl C G, Barnes P J, Chung K F
Department of Thoracic Medicine, National Heart and Lung Institute and Brompton Hospital, London, U.K.
Eur J Pharmacol. 1991 Jan 25;193(1):35-9. doi: 10.1016/0014-2999(91)90197-x.
We studied the effects of inhaled formoterol (0.75 mg/ml, 60 breaths = 26 micrograms), a long-acting beta 2-adrenoceptor agonist, or of the more short-acting drug, salbutamol (25 mg/ml, 60 breaths = 875 micrograms), on acute airflow obstruction and airway microvascular leakage (MVL) induced by inhaled histamine in anesthetized guinea pigs. Lung resistance (RL) and its recovery following hyperinflation (recovery RL) were measured for 6 min after histamine (1 or 2 mg/ml, 30 breaths) in animals pretreated with either inhaled beta 2-adrenoceptor agonist or inhaled saline (0.9%, 60 breaths). MVL was measured by determining the amount of extravasated Evans blue dye at various airway levels. Histamine increased RL dose dependently with a mean peak RL (+/- S.E.M.) of 13.1 +/- 2.41 cmH2O/ml per s after 2 mg/ml of histamine. Both formoterol and salbutamol significantly inhibited both peak and recovery RL and MVL to a similar degree. There was a significant correlation between the degree of extravasated dye and both peak and recovery RL, suggesting that MVL partly contributes to histamine-induced airflow obstruction. Formoterol is approximately 35 times more potent than salbutamol to inhibit both MVL and airflow obstruction induced by histamine aerosol.
我们研究了吸入长效β2肾上腺素能受体激动剂福莫特罗（0.75毫克/毫升，60次呼吸=26微克）或短效药物沙丁胺醇（25毫克/毫升，60次呼吸=875微克）对麻醉豚鼠吸入组胺所致急性气流阻塞和气道微血管渗漏（MVL）的影响。在用吸入β2肾上腺素能受体激动剂或吸入生理盐水（0.9%，60次呼吸）预处理的动物中，在给予组胺（1或2毫克/毫升，30次呼吸）后6分钟测量肺阻力（RL）及其在过度充气后的恢复情况（恢复性RL）。通过测定不同气道水平渗出的伊文思蓝染料量来测量MVL。组胺使RL剂量依赖性增加，在给予2毫克/毫升组胺后，平均峰值RL（±标准误）为13.1±2.41厘米水柱/毫升每秒。福莫特罗和沙丁胺醇均能显著抑制峰值和恢复性RL以及MVL，且程度相似。渗出染料的程度与峰值和恢复性RL之间存在显著相关性，表明MVL部分导致了组胺诱导的气流阻塞。福莫特罗抑制组胺气雾剂诱导的MVL和气流阻塞的效力约为沙丁胺醇的35倍。
