MECHANISMS OF VERAPAMIL INHIBITION OF BRONCHOSPASM

维拉帕米抑制支气管痉挛的机制

• 批准号: 3343526
• 负责人: GILBERT A RINARD
• 金额: $ 5.64万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-04-01 至 1987-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3343526
• 关键词: aerosols; allergens; antiadrenergic agents; antiallergic agents; antihistamines; asthma; bronchospasm; disease /disorder model; drug interactions; drug metabolism; helminthic antigen; high performance liquid chromatography; nerve endings; neural transmission; neuropharmacology; parasympathetic nervous system; pentobarbital; reflex; respiratory airway pressure; respiratory muscles; verapamil

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.

我们已经证明维拉帕米能够消除抗原诱导