ANGIOTENSIN-CONVERTING ENZYME-INHIBITORS CAN POTENTIATE OZONE-INDUCEDAIRWAY HYPERRESPONSIVENESS

We investigated the effects of single and chronic oral administration of angiotensin-converting enzyme inhibitors on ozone-induced airway hy perresponsiveness in guinea pigs. Ozone exposure (3 ppm for 2 h) signi ficantly increased airway responsiveness in vehicle-treated animals an d in animals with either single or chronic administration (8 days) of drugs. Single administration of imidapril, enalapril and captopril sig nificantly potentiated ozone-induced airway hyperresponsiveness at a d ose of 100, 50 and 50 mg/kg, respectively, although these doses did no t influence airway responsiveness in normal guinea pigs, i.e., the mag nitude of potentiation was captopril > enalapril > imidapril. In the s tudy of chronic administration of the drugs, imidapril (10-100 mg/kg p er day) had no influence on airway responsiveness in both normal and o zone-treated animals. In contrast, captopril and enalapril (10-100 mg/ kg per day) dose-dependently potentiated ozone-induced airway hyperres ponsiveness, with no influence on airway responsiveness in normal anim als. That is, the magnitude was enalapril > captopril. These results i ndicate that angiotensin-converting enzyme inhibitors potentiate airwa y responsiveness in ozone-treated guinea pigs but not in normal guinea pigs and that imidapril is less potent than enalapril and captopril i n potentiating ozone-induced airway hyperresponsiveness in guinea pigs . (C) 1997 Elsevier Science B.V.