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.