Angiotensin-converting enzyme inhibitors can potentiate ozone-induced airway hyperresponsiveness.
We investigated the effects of single and chronic oral administration of angiotensin-converting enzyme inhibitors on ozone-induced airway hyperresponsiveness in guinea pigs. Ozone exposure (3 ppm for 2 h) significantly increased airway responsiveness in vehicle-treated animals and in animals with either single or chronic administration (8 days) of drugs. Single administration of imidapril, enalapril and captopril significantly potentiated ozone-induced airway hyperresponsiveness at a dose of 100, 50 and 50 mg/kg, respectively, although these doses did not influence airway responsiveness in normal guinea pigs, i.e., the magnitude of potentiation was captopril > enalapril > imidapril. In the study of chronic administration of the drugs, imidapril (10-100 mg/kg per day) had no influence on airway responsiveness in both normal and ozone-treated animals. In contrast, captopril and enalapril (10-100 mg/kg per day) dose-dependently potentiated ozone-induced airway hyperresponsiveness, with no influence on airway responsiveness in normal animals. That is, the magnitude was enalapril > captopril. These results indicate that angiotensin-converting enzyme inhibitors potentiate airway responsiveness in ozone-treated guinea pigs but not in normal guinea pigs and that imidapril is less potent than enalapril and captopril in potentiating ozone-induced airway hyperresponsiveness in guinea pigs.
Matsubara
S
S
Lead Optimization Research Laboratory, Tanabe Seiyaku Co., Ltd., Toda, Saitama, Japan. s-matsu@tanabe.co.jp
Kikkawa
H
H
Kaminuma
O
O
Ikezawa
K
K
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000503:physiopathology*; D002216:Captopril / Q000008:administration & dosage / Q000494:pharmacology; D004357:Drug Synergism; D004656:Enalapril / Q000008:administration & dosage / Q000494:pharmacology; D006168:Guinea Pigs; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology; D048289:Imidazolidines; D008297:Male; D010126:Ozone / Q000633:toxicity*; D012129:Respiratory Function Tests
D000806:Angiotensin-Converting Enzyme Inhibitors; D007093:Imidazoles; D048289:Imidazolidines; D010126:Ozone; D004656:Enalapril; D002216:Captopril; C065166:imidapril