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Am J Physiol Regul Integr Comp Physiol 292: R2400-R2405, 2007. First published February 15, 2007; doi:10.1152/ajpregu.00791.2006
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WATER AND ELECTROLYTE HOMEOSTASIS

Effects of 20-HETE on Na+ transport and Na+-K+-ATPase activity in the thick ascending loop of Henle

Ming Yu,1 Bernardo Lopez,1,3 Elisabete A. Dos Santos,1 John R. Falck,4 and Richard J. Roman1,2,3

Departments of 1Physiology and 2Medicine and 3Kidney Disease Center, Medical College of Wisconsin, Milwaukee, Wisconsin; 4Department of Biochemistry and Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas

Submitted 10 November 2006 ; accepted in final form 9 February 2007

Previous studies have indicated that 20-hydroxyeicosatetraenoic acid (20-HETE) inhibits Na+ transport in the medullary thick ascending loop of Henle (mTALH), but the mechanisms involved remain uncertain. The present study compared the effects of 20-HETE with those of ouabain and furosemide on intracellular Na+ concentration ([Na+]i), Na+-K+-ATPase activity, and 86Rb+ uptake, an index of Na+ transport, in mTALH isolated from rats. Ouabain (2 mM) increased, whereas furosemide (100 µM) decreased, [Na+]i in the mTALH of rats. Ouabain and furosemide inhibited 86Rb+ uptake by 91 and 30%, respectively. 20-HETE (1 µM) had a similar effect as ouabain and increased [Na+]i from 19 ± 1 to 30 ± 1 mM. 20-HETE reduced Na+-K+-ATPase activity by 30% and 86Rb+ uptake by 37%, but it had no effect on 86Rb+ uptake or [Na+]i in the mTALH of rats pretreated with ouabain. 20-HETE inhibited 86Rb+ uptake by 12% and increased [Na+]i by 19 mM in mTALH pretreated with furosemide. These findings indicate that 20-HETE secondarily inhibits Na+ transport in the mTALH of the rat, at least, in part by inhibiting the Na+-K+-ATPase activity and raising [Na+]i.

cytochrome P-4504A; 20-hydroxyeicosatetraenoic acid; sodium-potassium-adenosinetriphosphatase; medullary thick ascending loop of Henle; kidney; rat



Address for reprint requests and other correspondence: R. J. Roman, Dept. of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226 (e-mail: rroman{at}mcw.edu)







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