MECHANISMS OF VERAPAMIL INHIBITION OF BRONCHOSPASM

我们已经证明了维拉帕米有能力消除抗原诱导 支气管痉挛。相比之下，维拉帕米仅有效地减弱了 组胺引起的最大气道阻力增加。这些发现 对其作用机制有重要的影响 维拉帕米，提示除呼吸道通畅外的其他部位的主要作用 肌肉。 这个项目的总体目标是确定主要的行动模式 维拉帕米影响犬哮喘模型中的支气管收缩。 这项研究的第一个目标将是确定维拉帕米是否可以抑制 组胺的释放，也许还有其他即刻的调解人 过敏症。蛔虫期间将采集动脉血样本 过敏性犬血清抗原(ASA)气雾剂攻击前后的变化 维拉帕米治疗。血清组胺水平将由高水平的 加压液相色谱和/或化学分析。 第二个目标将是确定迷走神经反射是否在 我们的过敏性支气管收缩模型。双侧迷走神经阻滞会 在阿司匹林和组胺支气管激发时产生。此外， 戊巴比妥钠麻醉效果的对照研究 使用氯醛糖作为主要麻醉剂的实验。 第三个目标将是测试维拉帕米可以抑制 内侧副交感神经节和神经末梢的乙酰胆碱释放 呼吸道的平滑肌肉。将进行频率/响应测量 电场刺激体外培养的气管肌条的实验研究 维拉帕米的存在和不存在。

We have demonstrated verapamil's ability to abolish antigen-induced bronchospasm. In contrast, verapamil was effective in only attenuating the maximal increase in airway resistance induced by histamine. These findings have important implications concerning the mechanism of action of verapamil, suggesting major action at a site other than airway smooth muscle. The overall goal of this project is to determine the major mode of action of verapamil as it affects bronchoconstriction in a canine asthma model. The first aim of this study will be to determine if verapamil can inhibit the release of hisamine and perhaps other mediators of immediate hypersensitivity. Arterial blood samples will be collected during Ascaris suum antigen (ASA) aerosol challenges of allergic dogs before and after verapamil treatment. Serum histamine levels will be determined by high pressure liquid chromatography and/or by chemical assay. The second aim will be to determine if vagal reflexes play a major role in our model of allergic bronchoconstriction. Bilateral vagal blockade will be produced during ASA and histamine bronchoprovocation. In addition, the effects of pentobarbital anesthesia will be examined by conducting control experiments in which chloralose is utilized as the primary anesthetic agent. The third aim will be a test of the hypothesis that verapamil can inhibit acetylcholine release from parasympathetic ganglia and nerve endings within the airway smooth muscle. Frequency/response measurements will be made during electrical field stimulation of trachealis muscle strips in vitro in the presence and absence of verapamil.