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• W2047320029 abstract "Superoxide (O 2 − ) increases Na + reabsorption in the thick ascending limb (THAL) by enhancing Na/K/2Cl cotransport. However, the effects of O 2 − on other THAL transporters, such as Na + /H + exchangers, are unknown. We hypothesized that O 2 − stimulates Na + /H + exchange in the THAL. We assessed total Na + /H + exchange activity by measuring recovery of intracellular pH (pH i ) after acid loading in isolated perfused THALs before and after adding xanthine oxidase (XO) and hypoxanthine (HX). We found that XO and HX decreased total pH i recovery rate from 0.26 ± 0.05 to 0.21 ± 0.04 pH units/min ( P < 0.05), and this net inhibition decreased steady-state pH i from 7.52 to 7.37. Because THALs have different Na + /H + exchanger isoforms on the luminal and basolateral membrane, we tested the effects of xanthine oxidase and hypoxanthine on luminal and basolateral Na + /H + exchange by adding dimethylamiloride to either the bath or lumen. Xanthine oxidase and hypoxanthine increased luminal Na + /H + exchange from 3.5 ± 0.8 to 6.7 ± 1.4 pmol·min −1 ·mm −1 ( P < 0.01) but decreased basolateral Na + /H + exchange from 10.8 ± 1.8 to 6.8 ± 1.1 pmol·min −1 ·mm −1 ( P < 0.007). To ascertain whether these effects were caused by O 2 − or H 2 O 2 , we examined the ability of tempol, a superoxide dismutase mimetic, to block these effects. In the presence of tempol, xanthine oxidase and hypoxanthine had no effect on luminal or basolateral Na + /H + exchange. We conclude that O 2 − inhibits basolateral and stimulates luminal Na + /H + exchangers, perhaps because different isoforms are expressed on each membrane. Inhibition of basolateral Na + /H + exchange may enhance stimulation of luminal Na + /H + exchange by providing additional protons to be extruded across the luminal membrane. Together, the effects of O 2 − on Na + /H + exchange may increase net HCO 3 − reabsorption by the THAL." @default.
• W2047320029 created "2016-06-24" @default.
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• W2047320029 creator A5072291294 @default.
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• W2047320029 date "2006-01-01" @default.
• W2047320029 modified "2023-10-14" @default.
• W2047320029 title "Differential effects of superoxide on luminal and basolateral Na⁺/H⁺ exchange in the thick ascending limb" @default.
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• W2047320029 doi "https://doi.org/10.1152/ajpregu.00447.2005" @default.
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