Mirza Z N, Tokuyama K, Arakawa H, Kato M, Mochizuki H, Morikawa A
Department of Paediatrics, Gunma University School of Medicine, Maebashi, Japan.
Clin Exp Allergy. 1998 May;28(5):644-52. doi: 10.1046/j.1365-2222.1998.00263.x.
Beta2-adrenoceptor agonists (beta2-agonists) are shown to inhibit airway microvascular leakage in experimental animals. This effect may change in animals with chronic airway inflammation.
We examined whether inhaled beta2-agonists inhibit microvascular leakage in guinea-pig airways with chronic allergic inflammation.
Three weeks after the sensitization with ovalbumin (OA; 6 mg/mL), each guinea pig was challenged with inhaled OA once a day for 1 or 3 weeks. Control animals without sensitization with OA also inhaled vehicle for OA (saline) for 3 weeks. One day after the last challenge, different doses of inhaled procaterol (1, 3 or 10 microg/mL) or vehicle was given to animals for 10 min after an anaesthesia. Fifteen minutes after the end of inhalation, the animals were given i.v. Evans blue dye (EB dye; 20 mg/kg), a marker of microvascular leakage, and then i.v. histamine (3 or 30 microg/kg) or vehicle. Lung resistance, a parameter of airflow obstruction, was measured for 6 min and the lungs were removed to calculate the amount of extravasated EB dye into the airways.
A significant increase in eosinophil infiltration into the airways was seen in sensitized and challenged animals compared with control animals without sensitization. Among animals receiving antigenic exposure for either 0 (control), 1 or 3 weeks, 10 microg/mL procaterol significantly inhibited 30 microg/kg histamine-induced increase in EB dye extravasation to a similar degree (ranged from 28.7 to 69.8% inhibition) as well as that in lung resistance (more than 90% inhibition in all groups). The minimal dose of procaterol to inhibit 3 microg/kg histamine-induced microvascular leakage was not different between nonsensitized control animals and those sensitized and challenged for 3 weeks at all airway levels.
Inhaled beta2-adrenoceptor agonists may be also potent in attenuating microvascular leakage even in the airways with chronic allergic inflammation.
β2肾上腺素能受体激动剂（β2激动剂）在实验动物中可抑制气道微血管渗漏。在患有慢性气道炎症的动物中，这种效应可能会发生变化。
我们研究了吸入性β2激动剂是否能抑制慢性过敏性炎症豚鼠气道中的微血管渗漏。
用卵清蛋白（OA；6mg/mL）致敏3周后，每只豚鼠每天吸入OA进行激发，持续1周或3周。未用OA致敏的对照动物也吸入OA的赋形剂（生理盐水）3周。在最后一次激发后1天，麻醉动物后给予不同剂量的吸入性丙卡特罗（1、3或10μg/mL）或赋形剂，持续10分钟。吸入结束15分钟后，给动物静脉注射伊文思蓝染料（EB染料；20mg/kg），这是微血管渗漏的标志物，然后静脉注射组胺（3或30μg/kg）或赋形剂。测量气流阻塞参数肺阻力6分钟，然后取出肺脏以计算渗漏到气道中的EB染料量。
与未致敏的对照动物相比，致敏和激发的动物气道中嗜酸性粒细胞浸润显著增加。在接受抗原暴露0（对照）、1或3周的动物中，10μg/mL丙卡特罗显著抑制30μg/kg组胺诱导的EB染料外渗增加，抑制程度相似（范围为28.7%至69.8%），对肺阻力的抑制也相似（所有组均超过90%）。在所有气道水平，未致敏的对照动物与致敏并激发3周的动物相比，抑制3μg/kg组胺诱导的微血管渗漏所需的丙卡特罗最小剂量无差异。
即使在患有慢性过敏性炎症的气道中，吸入性β2肾上腺素能受体激动剂在减轻微血管渗漏方面也可能有效。
