Relationship between sodium transmembrane fluxes and methacholine-provoked bronchoconstriction

Abstract

Sodium transmembrane flux modifies cell membrane potential by changing intracellular ion concentration and amino-acid balance, thereby influencing cell reactivity. Diminished activity of Na +-K + -2Cl - co-transport is a cause of primary hypertension. Furosemide is known to prevent methacholine-induced bronchoconstriction and inhibit Na +-K +-2Cl - co-transport. A possible mechanism of this protective effect is furosemide-dependent inhibition of ion transport in cell membrane, but data from previous studies are contradictory. We therefore investigated the correlation between the sodium flux in lymphocytes of asthmatics and the results of methacholine challenge. Fifteen patients with mild asthma, (seven males, eight females, age: 18–52, mean: 30.67 years), were included in the study. Patients underwent two methacholine challenge tests on two separate occasions. The second methacholine nebulisation was preceded by nebulisation with 20 mg of furosemide. The in vitro Na +-K +-2Cl - co-transport activity was investigated in peripheral blood lymphocytes using 22Na. There was no statistically significant difference between methacholine-induced bronchoconstriction (PC20) with and without furosemide nebulisation ( P = 0.73) . The value of PC20 without furosemide prenebulisation correlated with both Na +-K +-2Cl - co-transport activity (R = 0.684 ; P = 0.005) and total sodium flux (R = 0.618 ; P = 0.014). When methacholine challenge was preceded by inhalation with furosemide, there were no correlations between methacholine PC20 and either Na +-K +-2Cl - co-transport activity (R = 0.104 ; P = 0.719) or total sodium flux (R = 0.062 ; P = 0.826). In conclusion, methacholine-induced bronchoconstriction is not prevented by prenebulisation with furosemide; methacholine-induced bronchoconstriction is interrelated with transmembrane sodium ion fluxes, both total sodium flux and furosemide-dependent sodium flux (Na +-K +-2Cl - co-transport). The nature of this relationship remains unclear.