Importance of calcium in citric acid-induced airway constriction.
In previous studies, a 5-min inhalational challenge with 10% citric acid aerosol (0.52 M) elicited bronchoconstriction in Basenji-Greyhound (BG) dogs with hyperreactive airways but not in mongrel dogs. This response was independent of vagal reflexes because it was not attenuated by atropine. Citric acid might elicit bronchoconstriction because of acidity, calcium chelation, or some other effect of the citrate molecule. To assess these factors, barbiturate-anesthetized BG dogs were challenged (5 min) with aerosols of 10% acetic acid or a citric acid (0.48 M)/Na3citrate (0.04 M) mixture of equivalent pH, 6% Na2-ethylenediaminetetraacetic acid (EDTA), or 6% CaNa2EDTA. Each challenge was delivered in a separate week. The acidity alone was not an adequate stimulus, since pulmonary resistance (RL) was unaltered by 10% acetic acid, although markedly increased by the citric acid-Na3citrate mixture [2.2 +/- 0.4 (SE) cmH2O X l-1 X s prechallenge, 10.0 +/- 2.2 postchallenge]. Aerosols of Na2EDTA provoked a similar increase in RL (2.1 +/- 0.4 cmH2O X l-1 X s prechallenge, 9.0 +/- 1.8 postchallenge). Neither effect was attenuated by intravenous atropine (0.2 mg/kg). CaNa2EDTA caused no changes in RL. We conclude that it is the calcium chelating action of citric acid rather than its acidity that is responsible for bronchoconstriction in BG dogs with hyperreactive airways.
D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001985:Bronchial Provocation Tests; D001986:Bronchial Spasm / Q000139:chemically induced* / Q000503:physiopathology; D002118:Calcium / Q000502:physiology; D002951:Citrates / Q000494:pharmacology*; D019343:Citric Acid; D004285:Dogs; D004492:Edetic Acid / Q000494:pharmacology; D008170:Lung Compliance / Q000187:drug effects
D002951:Citrates; D019343:Citric Acid; D001285:Atropine; D004492:Edetic Acid; D002118:Calcium