ATP causes neurogenic bronchoconstriction in the dog

✍ Scribed by Guennadi Katchanov; Jiang Xu; Edward S. Schulman; Amir Pelleg

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 263 KB
• Volume: 45
• Category: Article
• ISSN: 0272-4391
• DOI: 10.1002/(sici)1098-2299(199811/12)45:3/4<342::aid-ddr34>3.0.co;2-p

✦ Synopsis

Adenosine 5¢-triphosphate (ATP) causes bronchoconstriction in normal and asthmatic human subjects. The mechanism of this action is not known. Because ATP is known to elicit vagal afferent neural traffic by stimulating pulmonary vagal C-fiber terminals, we have hypothesized that this action of ATP results in reflex bronchoconstriction. To test this hypothesis, ATP, adenosine, and capsaicin were administered as rapid boluses into the right atrium of anesthetized dogs (n = 8) before and after either atropine or bilateral cervical vagotomy. ATP and adenosine were given also in the presence of physostigmine to accentuate vagal input into the lungs. Fluoroscopic visualization of the bronchial tree was achieved by insufflation of heavy metal powder into the lungs. Bronchi diameters were determined using bronchograms. Pulmonary dynamics were quantitated using tracheal and esophageal pressures and respiratory air flow. ATP, adenosine, and capsaicin caused bronchoconstriction that was eliminated by either atropine or vagotomy. The effect of ATP was much more pronounced (P < 0.05) than that of adenosine and capsaicin: the diameter of generation III bronchi of 6.8 ± 0.8 mm was reduced by 27.5 ± 2.1%, 10.0 ± 2.1%, and 15.4 ± 3.3% by ATP, adenosine, and capsaicin, respectively. Similarly, in the presence of physostigmine, lung resistance of 2.67 ± 0.24 mmH 2 O/l per min and 2.76 ± 0.20 was increase by 68 ± 25% and 16 ± 12% by ATP and adenosine, respectively (P < 0.05). Because endogenous ATP is released into the extracellular space under physiologic and pathophysiologic conditions, the present data indicated that endogenous ATP could trigger neurogenic bronchoconstriction and thereby play a mechanistic role in obstructive airway diseases in general and asthma in particular.