FUROSEMIDE-INDUCED AIRWAY RELAXATION IN GUINEA-PIGS - RELATION TO NA-K-2CL COTRANSPORTER FUNCTION

This study tested the hypothesis that airway relaxation to furosemide is mediated via the Na-K-2Cl cotransporter. If this mechanism exists i n airway smooth muscle like in vascular smooth muscle, changes in airw ay relaxation should be associated with changes in Na-K-2Cl cotranspor ter function, and both should be substrate dependent. Tracheal rings f rom newborn guinea pigs were bathed in standard (STD) or varying low C l- concentration ([Cl-]) N-2-hydroxyethylpiperazine-N'-2-ethanesolfoni c acid (HEPES). Isometric relaxation to 300 mu M furosemide or 10(-8) to 10(-5) M salbutamol was measured. Airway segments were incubated wi th rubidium-86 (Rb-86) in STD or varying low [Cl-] HEPES, with and wit hout 300 mu M furosemide or 25 mu M salbutamol. Furosemide was unable to reduce Rb-86 uptake at 10 mM [Cl-], although relaxation was still o bserved in 10 mM [Cl-]. Salbutamol did not affect Rb-86 uptake. This s tudy demonstrated that there is a furosemide-sensitive Na-K-2Cl cotran sporter in newborn guinea pig trachea. However, the effect of furosemi de on cotransporter function did not always directly correspond to dif ferences in relaxation, suggesting that the Na-K-2Cl cotransporter may play a major, but not exclusive, role in furosemide-induced airway re laxation.