Basis of Rise in Intracellular Sodium in Airway Hyperresponsiveness and Asthma

Abstract

The aim of this study was to investigate the basis of disturbances in sodium transport in asthma and in airway hyperresponsiveness without symptoms of asthma (asymptomatic AHR). We measured the intracellular sodium (Na(i)); activity of Na(+)/K(+)-ATPase in unstimulated cells (resting activity) and in cell homogenate under optimal conditions (maximal activity); and sodium influx, in mixed leukocytes of 15 normal subjects, 12 subjects with asymptomatic AHR, and 26 asthmatics with or without active symptoms. Resting Na(+)/K(+)-ATPase activity was the same as sodium influx, consistent with homeostasis. Compared with normal subjects, those with asymptomatic AHR or asthma with controlled symptoms had a twofold increase in sodium influx and Na(i). Symptomatic asthmatics also had a twofold increase in sodium influx but a fourfold elevation of Na(i). Maximal Na(+)/K(+)-ATPase activity was reduced by half in symptomatic asthmatics compared with normal subjects. The reduction of maximal Na(+)/K(+)-ATPase activity was associated with a significant decrease in ATP turnover per Na(+)/K(+)-ATPase molecule but not number of Na(+)/K(+)-ATPase molecules per cell. In summary, airway hyperresponsiveness with or without asthma is associated with increased sodium influx and Na in leukocytes. Resting activity of Na(+)/K(+)-ATPase is also increased as a compensatory response to the increased sodium influx, but it is achieved at the expense of higher Na(i). Symptomatic asthma is additionally associated with reduction in maximal activity of Na(+)/K(+)-ATPase, resulting in reduced capacity to handle the increase in sodium influx and consequent severe elevations in Na(i).

Sodium and asthma: something borrowed, something new?

“…This finding was supported by a barrage of studies that suggested the existence of a serum-borne inhibitor of the Na ϩ /K ϩ pump in subjects with allergic rhinitis and/or allergic asthma (3,13,23,54,55,64). This unknown factor increased intracellular [Na ϩ ], decreased uptake of Rb ϩ , and decreased overall activity of the Na ϩ /K ϩ pump in isolated human platelet, leukocytes, and peripheral blood mononuclear cells (3,13,23,54,55,62,64). Furthermore, the plasma from allergic individuals could inhibit Rb ϩ uptake in leukocytes from control (i.e., nonallergic) individuals.…”

“…The magnitude of this effect was well associated with the degree of airway dysfunction in the donor subjects (62). These data were confirmed by two more recent studies that reported an association between Na ϩ /K ϩ pump inhibition and resulting intracellular Na ϩ accumulation and increased severity of airway dysfunction (3,13).…”

Cellular Na+ handling mechanisms involved in airway smooth muscle contraction (Review)

“…This pump is very sensitive to inhibition by cardioactive steroids, particularly the group of digitalis and ouabain used to treat congestive heart failure and arrhythmias (20). Abundant sources report the presence of a 'serum factor' (most probably ouabain) that inhibits the function of NKA (21–26). Endogenous ouabain has been characterized as a steroidal glycoside found in blood plasma and is synthesized by the adrenal glands, hypothalamus and pituitary (27–33).…”

“…Multiple studies of patients with atopic asthma and/or allergic rhinitis report the presence of plasmatic, endogenous ouabain, indicating a probable intracellular Na + accumulation (21–26). In fact, the study by Tribe et al (25) shows an increased intracellular Na + concentration in mononuclear cells from healthy individuals incubated with plasma of asthmatic blood donors.…”

Features of coupled Na+, K+, 2Cl–-cotransport with erythrocyte β-adrenergic system in bronchial asthma

“…Изучению активности транспортных систем Na + и K + у больных с бронхолегочной патологией и, в част ности, с бронхиальной астмой (БА) был посвящен ряд исследований как в нашей стране [1,2], так и за рубежом [3,4]. На рубеже XIX-XX вв.…”