Additive Effect of Chronic Hypoxia and Aldosterone on Electrogenic Sodium Transport in Rat Rectal Epithelium

Abstract

Abbreviations: ENaC, epithelial sodium channel; I SC , shortcircuit current; QO 2 , oxygen consumption rate IntroductionA remarkable functional feature of the intestinal epithelium is its normally low oxygen pressure, a condition that has been dubbed "physiological hypoxia". 1 The colonic epithelium reabsorbs about 90% of the water contained in the chime flowing through the ileocecal valve and modifies its electrolyte composition, with net sodium and chloride absorption and net potassium and bicarbonate excretion. Fecal dehydration is closely linked to sodium and chloride absorption, because the latter provides the driving force for the former. 2,3 Although sodium and chloride absorption occurs throughout the colon, the precise mechanisms are different along the various colonic segments.3 There are also differences between species. For example, in the rabbit and human distal colon, sodium absorption is an electrogenic process, dependent on apical epithelial sodium channels (ENaC) which are sensitive to low concentrations of amiloride. 4-6However, in the rat distal colon, sodium absorption is normally insensitive to amiloride, occurring as an electroneutral process dependent on coupled apical Na + /H + and Cl -/HCO 3 -exchangers. 7-9Nevertheless, ENaCs are expressed at the apical membrane of the rat distal colon epithelium. 10,11The colonic epithelium is, like other sodium transporting epithelia, a classical target for aldosterone and related mineralocorticoid hormones. 12 In the rat distal colon, mineralocorticoids not only increase net sodium absorption but also cause a switch in its underlying mechanism, from electroneutral to electrogenic, mediated by functional ENaCs. This change may be brought about by increased endogenous secretion of aldosterone in response to a low-sodium diet, 13 by administration of natural or synthetic mineralocorticoids, 14 and also by incubation of the epithelium with physiological concentrations of aldosterone in vitro. 15 This aldosterone-induced electrogenic sodium transport is associated with increased epithelial oxygen consumption, and both effects are blocked by amiloride. 16On the other hand, chronic hypobaric hypoxia also induces electrogenic sodium transport in the rat distal colon, 17 although it does not increase QO 2 .18 It is highly unlikely that this response is mediated AbstractBackground: Both chronic hypoxia and mineralocorticoids independently stimulate electrogenic sodium absorption in rat distal colon. It is hitherto unknown whether there is any interaction between these two stimuli. The aim of this work was to assess the interaction of these stimuli on rat rectal epithelium in vitro.Methods: Isolated rectal mucosa samples were obtained from adult rats submitted to hypobaric hypoxia for 10 days or breathing at normal pressure. Tissues were mounted in Ussing chambers which allow simultaneous measurement of short-circuit current (ISC) and oxygen consumption rate (QO2). Both variables were measured at baseline, after 8 h-incubation with aldosterone (10 nM) and afte...