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

Abstract

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, and86Rb+uptake, an index of Na+transport, in mTALH isolated from rats. Ouabain (2 mM) increased, whereas furosemide (100 μM) decreased, [Na+]iin the mTALH of rats. Ouabain and furosemide inhibited86Rb+uptake by 91 and 30%, respectively. 20-HETE (1 μM) had a similar effect as ouabain and increased [Na+]ifrom 19 ± 1 to 30 ± 1 mM. 20-HETE reduced Na+-K+-ATPase activity by 30% and86Rb+uptake by 37%, but it had no effect on86Rb+uptake or [Na+]iin the mTALH of rats pretreated with ouabain. 20-HETE inhibited86Rb+uptake by 12% and increased [Na+]iby 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.