MECHANISMS OF VERAPAMIL INHIBITION OF BRONCHOSPASM

我们已经证明维拉帕米能够消除抗原诱导的 支气管痉挛 与此相反，维拉帕米仅能有效地减弱 组胺引起的气道阻力最大增加。 这些发现 对药物的作用机制有重要影响， 维拉帕米，提示主要作用于除气道通畅以外的部位 肌肉. 本项目的总体目标是确定主要的行动方式 异搏定影响犬哮喘模型的支气管收缩。 本研究的第一个目的是确定维拉帕米是否能抑制 组胺的释放和其他可能的立即 超敏反应 在蛔虫期间将采集动脉血样本 猪抗原（阿萨）气溶胶激发过敏犬前后 维拉帕米治疗 血清组胺水平将通过高 压力液相色谱法和/或化学分析法。 第二个目的是确定迷走神经反射是否在神经系统的病理生理过程中起主要作用。 我们的过敏性支气管收缩模型 双侧迷走神经阻滞 在阿萨和组胺支气管激发期间产生。 此外该 戊巴比妥麻醉的效果将通过进行对照检查 使用氯醛糖作为主要麻醉剂的实验。 第三个目的是检验维拉帕米可以抑制 乙酰胆碱从副交感神经节和神经末梢内释放 气道平滑肌 将进行频率/响应测量 在电场刺激离体气管肌条时， 维拉帕米的存在与否

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.