Tachyphylaxis to furosemide in isolated airways of guinea pigs

This in vitro study was conducted to determine whether tachyphylaxis of guinea pig airway to furosemide occurs under conditions that produce tachyphylaxis to the beta 2-adrenoceptor agonist, salbutamol. Isometric 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 rings were first incubated with furosemide, 30 or 300 microM, or control for 60 min, washed, then constricted with 3 microM acetylcholine. At stable contraction, relaxation to furosemide (30 microM-1 mM) was measured. For comparison, similar experiments were performed with 10 microM salbutamol incubation for 30 min. 86Rb uptake, a marker for K+ transport and Na-K-Cl cotransport activity, was also measured in these airway segments. Pre-exposure to these airway relaxants did not affect contractile force generation by acetylcholine. Tracheal desensitization to both salbutamol and furosemide was observed. Partial recovery of furosemide induced relaxation was seen one hour after desensitization. Pre-exposure to 300 microM furosemide did not inhibit the decrease in 86Rb uptake normally observed with furosemide. In summary, we found that: 1) tachyphylaxis of guinea pig airway relaxation occurred with both salbutamol and furosemide under similar experimental conditions; however 2) inhibition of 86Rb uptake by furosemide was not affected by prior exposure. 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-sensitive Na-K-Cl cotransporter activity.