Yu Ming, Lopez Bernardo, Dos Santos Elisabete A, Falck John R, Roman Richard J
Departments of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Am J Physiol Regul Integr Comp Physiol. 2007 Jun;292(6):R2400-5. doi: 10.1152/ajpregu.00791.2006. Epub 2007 Feb 15.
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 microM) decreased, [Na+]i in the mTALH of rats. Ouabain and furosemide inhibited 86Rb+ uptake by 91 and 30%, respectively. 20-HETE (1 microM) 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.
以往研究表明，20-羟基二十碳四烯酸（20-HETE）可抑制髓袢升支粗段（mTALH）中的Na⁺转运，但其中涉及的机制仍不明确。本研究比较了20-HETE与哇巴因和呋塞米对从大鼠分离出的mTALH中细胞内Na⁺浓度（[Na⁺]i）、Na⁺-K⁺-ATP酶活性以及作为Na⁺转运指标的⁸⁶Rb⁺摄取的影响。哇巴因（2 mM）可使大鼠mTALH中的[Na⁺]i升高，而呋塞米（100 μM）则使其降低。哇巴因和呋塞米分别抑制⁸⁶Rb⁺摄取91%和30%。20-HETE（1 μM）产生了与哇巴因类似的效应，使[Na⁺]i从19±1 mM升高至30±1 mM。20-HETE使Na⁺-K⁺-ATP酶活性降低30%，⁸⁶Rb⁺摄取降低37%，但对用哇巴因预处理的大鼠mTALH中的⁸⁶Rb⁺摄取或[Na⁺]i无影响。20-HETE使经呋塞米预处理的mTALH中的⁸⁶Rb⁺摄取降低12%，[Na⁺]i升高19 mM。这些发现表明，20-HETE至少部分地通过抑制Na⁺-K⁺-ATP酶活性并提高[Na⁺]i，继而抑制大鼠mTALH中的Na⁺转运。
