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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL032206-02
Application #
3343525
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1984-04-01
Project End
1987-03-31
Budget Start
1985-04-01
Budget End
1986-03-31
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Emory University
Department
Type
Schools of Medicine
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322