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Calcium channel blockers modulate airway constriction in the canine lung periphery
K S Lindeman1, C A Hirshman, A N Freed
1Department of Environmental Health Sciences, Johns Hopkins University, Baltimore, Maryland 21205.
Abstract:
We studied the effect of two voltage-sensitive calcium channel blockers on Na2EDTA-induced bronchoconstriction in the canine lung periphery. A wedged bronchoscope technique was used to measure collateral system resistance before and after challenges with aerosolized Na2EDTA, hypocapnia, aerosolized acetylcholine, and increased flow of dry air in anesthetized mongrel dogs. Nifedipine, a dihydropyridine calcium channel blocker, reduced hypocapnia-induced bronchoconstriction by 88 +/- 6% (SE) but did not alter Na2EDTA-induced constriction. Verapamil, a phenylalkylamine calcium channel blocker, attenuated hypocapnia- and Na2EDTA-induced bronchoconstriction by 69 +/- 6 and 44 +/- 7%, respectively, but did not significantly alter responses to either acetylcholine or dry air challenge. We conclude that calcium influx through voltage-sensitive calcium channels, perhaps of the T subtype, has a limited role in the initiation of Na2EDTA-induced bronchoconstriction in the canine lung periphery.
Insights
Voltage-sensitive calcium channel blockers had varied effects on canine lung constriction. Verapamil partially reduced Na2EDTA-induced constriction, while nifedipine did not, suggesting limited calcium channel involvement in this specific response.
Area of Science:
- Pulmonary Physiology
- Pharmacology
- Respiratory Medicine
Background:
- Bronchoconstriction can be triggered by various stimuli, including chemical agents like disodium EDTA (Na2EDTA).
- Voltage-sensitive calcium channels (VSCCs) play a role in smooth muscle contraction, including in the airways.
Purpose of the Study:
- To investigate the role of VSCCs in Na2EDTA-induced bronchoconstriction in the canine lung periphery.
- To compare the effects of nifedipine and verapamil on different bronchoconstrictive stimuli.
Main Methods:
- Utilized a wedged bronchoscope technique in anesthetized dogs to measure collateral system resistance.
- Administered aerosolized Na2EDTA, induced hypocapnia, aerosolized acetylcholine, and dry air challenges.
- Assessed the impact of nifedipine (a dihydropyridine) and verapamil (a phenylalkylamine) on these induced responses.
Main Results:
- Nifedipine significantly reduced hypocapnia-induced bronchoconstriction (88%) but had no effect on Na2EDTA-induced constriction.
- Verapamil attenuated hypocapnia-induced (69%) and Na2EDTA-induced (44%) bronchoconstriction.
- Neither blocker affected responses to acetylcholine or dry air challenges.
Conclusions:
- Calcium influx via VSCCs plays a limited role in initiating Na2EDTA-induced bronchoconstriction in the canine lung periphery.
- Different subtypes of VSCCs may be involved in mediating responses to various bronchoconstrictive stimuli.