ACUTE HYPEROXIC INJURY ATTENUATES THE RELAXING EFFECTS OF LOOP DIURETICS AND SALBUTAMOL ON LARGE AIRWAYS OF NEWBORN GUINEA-PIGS

We have previously found an age-dependent relaxing effect of furosemid e in normal fetal, newborn, and adult guinea pig airways with fetal tr achea exhibiting the greatest relaxation and adult tissue the least. T his study was designed to expand upon this finding by determining if i n vivo hyperoxic exposure would influence in vitro airway relaxation m ediated by the loop diuretics, furosemide and ethacrynic acid, and the beta(2)-adrenoceptor agonist, salbutamol. Newborn guinea pigs were ra ised in >95% FiO(2) until ill; controls,in room air. Isometric relaxat ion to 3 X 10(-5) M furosemide, 3 X 10(-6) M ethacrynic acid, or 10(-8 )-10(-6) M salbutamol was recorded in 3 X 10(-6) M histamine-constrict ed airway rings. Ethacrynic acid, like furosemide, relaxed newborn gui nea pig airways. Hyperoxia did not alter the contractile effect of 3 X 10(-6) M histamine but did significantly decrease the relaxing effect of furosemide, ethacrynic acid, and salbutamol, Loop diuretic mediate d airway relaxation was accentuated in HEPES buffer when compared with Krebs, whereas salbutamol-mediated relaxation was unaffected. These r esults suggest that hyperoxia nonspecifically decreases airway respons iveness to the relaxing agents studied.