Airway hyperresponsiveness in neonatal chronic lung disease (CLD) is treated with both furosemide (FURO), a diuretic that inhibits the Na-K-2Cl cotransporter, and salbutamol (SAL), a β2-adrenoceptor agonist. This study was conducted to determine if the relaxation response in newborn guinea pig airway can be cross-desensitized to FURO and SAL in vitro. Trachea segments were suspended in HEPES buffer for measurement of isometric force. Segments were pre-treated with FURO (300 μM, 1 hr.) or SAL(10 μM, 30 min.). After pre-constriction with acetylcholine (3 μM), SAL or FURO was added at the same doses. Pre-treatment with FURO diminished relaxation to SAL [87±3% (n=11) vs 117±8% (n=10), p<0.05], as compared to saline-treated controls. Although relaxation to FURO was decreased by pre-treatment with SAL [47±2% (n=11) vs 73±3% (n=4), p<0.05], pre-treatment with DMSO (vehicle for SAL) alone [57±7%(n=6)] also inhibited FURO-mediated relaxation. 86Rb+ uptake(substitute for K+ transport via the Na-K-2Cl channel) was measured to determine if the mechanism of relaxation is related to changes in ion channel function. 86Rb+ uptake after pre-treatment with either SAL (n=7) or FURO (n=8) was not significantly altered during subsequent exposures, as compared to untreated controls. These results demonstrate that exposure to FURO desensitizes newborn guinea pig airway to SAL, and that the mechanism mediating this effect does not appear to be due to a lasting inhibition of Na-K-2Cl cotransporter activity. These findings suggest the need to consider whether such cross-desensitization of airway relaxation may occur in the treatment of neonatal CLD.
