Cross-Desensitization to Furosemide and Salbutamol in Isolated Neonatal Guinea Pig Airways

Abstract

Airway hyperresponsiveness in neonatal chronic lung disease is treated with both furosemide, a diurectic that inhibits the Na-K-2Cl cotrasporter, and salbutamol, a β₂-adrenoceptor agonist. Tachyphylaxis to both drugs in vitro has been described. This study was conducted to determine if the relaxation 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 isometric tension. Segments were pre-treated with either furosemide (300 μM, 1 h) or salbutamol (10 μM, 30 min). After constriction with 3 μM acetylcholine, relaxation response to salbutamol or furosemide, respectively, was measured. Pretreatment with furosemide diminished relaxation response to salbutamol [87 ± 3% (n = 11) vs. 117 ± 8% (n = 10), p < 0.05], as compared to saline-treated controls. In addition, pretreatment with salbutamol diminished 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 ⁸⁶Rb uptake, cyclic AMP levels and responses in the presence of charybdotoxin make it unlikely that Na-K-2Cl cotransporter activity, stimulation of cAMP, or opening of maxi-K⁺ channels are mechanisms involved in the cross-desensitization to furosemide and salbutamol in vitro.