Cross-desensitization to furosemide and salbutamol in isolated neonatal guinea pig airways

Airway hyperresponsiveness in neonatal chronic lung disease is treated with both furosemide, a diurectic that inhibits the Na-K-2Cl cotrasporter, and salbutamol, a beta(2)-adrenoceptor agonist. Tachyphylaxis to both drugs in vitro has been described. This study was conducted to determine if the rela xation response in newborn guinea pig airways to furosemide and salbutamol can be cross-desensitized in vitro. Tracheal ring segments from 4- to 7-day -old guinea pigs were suspended in HEPES buffer for measurement of isometri c tension. Segments were pretreated with either furosemide (300 mu M, 1 h) or salbutamol (10 mu M, 30 min). After constriction with 3 mu M acetylcholi ne, relaxation response to salbutamol or furosemide, respectively, was meas ured. Pretreatment with furosemide diminished relaxation response to salbut amol [87 +/- 3%(n = 11) vs. 117 +/- 8% (n = 10), p < 0.05], as compared to saline-treated controls. In addition, pretreatment with salbutamol diminish ed relaxation response to furosemide [53 +/- 2% (n = 11) vs. saline-treated (83 +/- 7%, n = 7, p < 0.05) and DMSO-treated controls (69 +/- 5%, n = 5, p < 0.05)]. Measurements of Rb-86 uptake, cyclic AMP levels and responses i n the presence of charybdotoxin make it unlikely that Na-K-2Cl cotransporte r activity, stimulation of cAMP, or opening of maxi-K+ channels are mechani sms involved in the cross-desensitization to furosemide and salbutamol in v itro.