HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 290/1/R79    most recent 00447.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Juncos, R. Articles by Garvin, J. L. Search for Related Content PubMed PubMed Citation Articles by Juncos, R. Articles by Garvin, J. L.

CALL FOR PAPERS
Cardiovascular-Kidney Interactions in Health and Disease

Differential effects of superoxide on luminal and basolateral Na⁺/H⁺ exchange in the thick ascending limb

¹Division of Hypertension and Vascular Research, Henry Ford Hospital, Detroit; and ²Department of Physiology, Wayne State University, Detroit, Michigan

Submitted 24 June 2005 ; accepted in final form 8 August 2005

Superoxide (O₂^–) increases Na⁺ reabsorption in the thick ascending limb (THAL) by enhancing Na/K/2Cl cotransport. However, the effects of O₂^– on other THAL transporters, such as Na⁺/H⁺ exchangers, are unknown. We hypothesized that O₂^– 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 O₂^– or H₂O₂, 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 O₂^– 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 O₂^– on Na⁺/H⁺ exchange may increase net HCO₃^– reabsorption by the THAL.

reactive oxygen species; intracellular pH; superoxide dismutase

This article has been cited by other articles:

				C. S. Wilcox Special feature: cardiovascular-kidney interactions in health and disease Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2006; 290(1): R34 - R36. [Full Text] [PDF]