Ozone increases susceptibility to antigen inhalation in allergic dogs.
To determine whether O3 exposure increased airway responsiveness to antigen inhalation, we studied airway responsiveness to acetylcholine (ACh) and Ascaris suum antigen (AA) before and after O3 in dogs both sensitive and insensitive to AA. Airway responsiveness was assessed by determining the provocative concentration of ACh and AA aerosols that increased respiratory resistance (Rrs) to twice the base-line value. O3 (3 parts per million) increased airway responsiveness to ACh in dogs both sensitive and insensitive to AA, and it significantly decreased the ACh provocation concentration from 0.541 +/- 0.095 to 0.102 +/- 0.047 (SE) mg/ml (P less than 0.01; n = 10). AA aerosols, even at the highest concentration in combination with O3, did not increase Rrs in dogs insensitive to AA. However, O3 increased airway responsiveness to AA in AA-sensitive dogs and significantly decreased log AA provocation concentration from 2.34 +/- 0.22 to 0.50 +/- 0.17 (SE) log protein nitrogen units/ml (P less than 0.01; n = 7). O3-induced hyperresponsiveness to ACh returned to the base-line level within 2 wk, but hyperresponsiveness to AA continued for greater than 2 wk. The plasma histamine concentration after AA challenge was significantly higher after than before O3 (P less than 0.01). Intravenous infusion of OKY-046 (100 micrograms.kg-1.min-1), an inhibitor of thromboxane synthesis, inhibited the O3-induced increase in responsiveness to ACh, but it had no effects on the O3-induced increase in responsiveness to AA and the increase in the plasma histamine concentration. These results suggest that O3 increases susceptibility to the antigen in sensitized dogs via a different mechanism from that of O3-induced muscarinic hyperresponsiveness.
Yanai
M
M
First Department of Internal Medicine and Pharmacology, School of Medicine, Tohoku University, Sendai, Japan.
Ohrui
T
T
Aikawa
T
T
Okayama
H
H
Sekizawa
K
K
Maeyama
K
K
Sasaki
H
H
Takishima
T
T
D000109:Acetylcholine / Q000494:pharmacology; D000336:Aerosols; D000403:Airway Resistance / Q000187:drug effects* / Q000276:immunology; D000818:Animals; D000947:Antigens, Helminth / Q000008:administration & dosage*; D001200:Ascaris / Q000276:immunology; D001249:Asthma / Q000209:etiology; D004285:Dogs; D005260:Female; D006632:Histamine / Q000097:blood; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D010126:Ozone / Q000633:toxicity*; D012882:Skin Tests; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D000336:Aerosols; D000947:Antigens, Helminth; D008689:Methacrylates; D010126:Ozone; D006632:Histamine; D013930:Thromboxane-A Synthase; C034364:ozagrel; D000109:Acetylcholine