Submit Manuscript | http://medcraveonline.com Abbreviations: ENaC, epithelial sodium channel; I SC , short- circuit current; QO 2 , oxygen consumption rate Introduction A 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 fowing through the ileocecal valve and modifes its electrolyte composition, with net sodium and chloride absorption and net potassium and bicarbonate excretion. 2 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. 4‒6 However, 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. 7‒9 Nevertheless, ENaCs are expressed at the apical membrane of the rat distal colon epithelium. 10,11 The 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. 16 On 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 MOJ Anat Physiol. 2017;4(4):331‒335. 331 ©2017 Saraví et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and build upon your work non-commercially. Additive effect of chronic hypoxia and aldosterone on electrogenic sodium transport in rat rectal epithelium Volume 4 Issue 4 - 2017 Fernando D Saraví, 1,2 María Isabel González Ruiz, 1 Graciela E Carra, 1 Jorge E Ibáñez 1,3 1 Faculty of Medical Sciences, National University of Cuyo, Argentina 2 Nuclear Medicine School, Argentina 3 Faculty of Medical Sciences, National University of Cuyo- CONICET, Argentina Correspondence: Fernando D Saraví, Instituto de Fisiología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Avenida del Libertador 50, Mendoza, MZ 5500, Argentina, Tel +542614135006, Ext 2756, Fax +542614614000, Email fernando.saravi@hotmail.es Received: July 27, 2017 | Published: November 03, 2017 Abstract Background: 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 after addition of the epithelial sodium channel, amiloride. Statistical analysis was performed with Student’s t tests and linear regression. Results: At baseline, samples from hypoxic rats had higher ISC (p=0.0002) but its QO2 did not differ from the control group (p=0.289). Incubation with aldosterone caused a progressive increase of ISC in both groups, but the difference in ISC between them was maintained throughout the incubation period. At the end of the incubation period, both groups showed significant increases in ISC and QO2. Amiloride reduced ISC and QO2 to the same extent in both groups. QO2 and ISC were linearly related to each other both at the baseline and at the end of the incubation period. Conclusion: While the rectal epithelium of chronically hypoxic rats had a higher ISC, its response of incubation with aldosterone at nanomolar concentration was preserved and followed the same time course than that of the rectal epithelium of non-hypoxic rats. Chronic hypoxia and aldosterone showed an additivity of effects in the rectal epithelium. The increase in ISC and QO2 caused by hypoxia and aldosterone was abolished by amiloride, suggesting an ENaC-dependent response to both stimuli. Keywords: aldosterone, amiloride, chronic hypoxia, oxygen consumption, rectal epithelium, sodium channel, ussing chamber MOJ Anatomy & Physiology Research Article Open Access