title: Calcium chelators induce bronchoconstriction in the canine lung periphery.
abstract: We studied the mechanism by which Na2EDTA, a divalent cation chelator, induces bronchoconstriction in the lung periphery of mongrel dogs as a model of nonspecific small airway hyperresponsiveness. Using a wedged bronchoscope technique, we measured collateral system resistance (Rcs) before and after challenges with aerosolized Na2EDTA. An isotonic solution (4% Na2EDTA, 0.28 osmol/kg) increased Rcs 91 +/- 21%. Na2EDTA increased Rcs in a dose-dependent fashion after challenges of increasing concentration (0, 1, 3, and 6%) or duration (15, 30, 60, and 90 s) with 6% Na2EDTA. Atropine (1 mg/kg iv) significantly (P = 0.01) attenuated the response to an aerosol challenge with distilled H2O. Atropine did not significantly (P = 0.35) alter the response to a challenge with 4% Na2EDTA. Challenge with 6% Na2EDTA (0.42 osmol/kg) increased Rcs to a significantly greater (P less than 0.01) extent than did challenge with 6% CaNa2EDTA (0.37 osmol/kg, 250 +/- 55 vs. 29 +/- 11%, respectively). We conclude that Na2EDTA induces bronchoconstriction in the canine lung periphery in a dose-dependent fashion. As suggested by the Na2EDTA-CaNa2EDTA comparison, hyperosmolality of the solution alone cannot explain this phenomenon. The mechanism does not depend on muscarinic activity and appears to involve chelation of calcium.
authors.affiliation: Department of Environmental Health Science, Johns Hopkins University, Baltimore, Maryland 21205.
authors.forename: K S
authors.initials: KS
authors.lastname: Lindeman
authors.forename: C A
authors.initials: CA
authors.lastname: Hirshman
authors.forename: A N
authors.initials: AN
authors.lastname: Freed
mesh_terms: D000403:Airway Resistance / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology*; D004285:Dogs; D004492:Edetic Acid / Q000494:pharmacology*; D008297:Male
chemical_list: D002614:Chelating Agents; D001285:Atropine; D004492:Edetic Acid; D002118:Calcium