TACHYPHYLAXIS TO FUROSEMIDE IN ISOLATED AIRWAYS OF GUINEA-PIGS

This in vitro study was conducted to determine whether tachyphylaxis o f guinea pig airway to furosemide occurs under conditions that produce tachyphylaxis to the beta(2)-adrenoceptor agonist, salbutamol. Isomet ric tension was measured in tracheal rings bathed in HEPES buffer from 4-6 d newborn guinea pigs of either sex, and 6 wk old males. Paired r ings were first incubated with furosemide, 30 or 300 mu M, or control for 60 min, washed, then constricted with 3 mu M acetylcholine. At sta ble contraction, relaxation to furosemide (30 mu M - 1 mM) was measure d. For comparison, similar experiments were performed with 10 mu M sal butamol incubation for 30 min. Rb-86 uptake, a marker for K+ transport and Na-K-Cl cotransport activity, was also measured in these airway s egments. Pre-exposure to these airway relaxants did not affect contrac tile force generation by acetylcholine. Tracheal desensitization to bo th salbutamol and furosemide was observed. Partial recovery of furosem ide induced relaxation was seen one hour after desensitization. Pre-ex posure to 300 mu M furosemide did not inhibit the decrease in Rb-86 up take normally observed with furosemide. In summary, we found that: 1) tachyphylaxis of guinea pig airway relaxation occurred with both salbu tamol and furosemide under similar experimental conditions; however 2) inhibition of Rb-86 uptake by furosemide was not affected by prior ex posure. Taken together, these results suggest that furosemide induced airway relaxation could be affected by repeated or prolonged exposure, but this response may not be associated with changes in furosemide-se nsitive Na-K-Cl cotransporter activity.