Ge Yuqiang, Huang Yufeng, Kohan Donald E
Division of Nephrology, University of Utah Health Sciences Center, 1900 East 30 North, Salt Lake City, UT 84132, USA.
Can J Physiol Pharmacol. 2008 Jun;86(6):329-36. doi: 10.1139/Y08-028.
Renal collecting duct (CD)-specific knockout of endothelin-1 (ET-1) causes hypertension and impaired Na excretion. A previous study noted failure to suppress the renin-angiotensin-aldosterone axis in these knockout (KO) mice, hence the current investigation was undertaken to examine the role of this system in CD ET-1 KO. Renal renin content was similar in kidneys from CD ET-1 KO and control mice during normal Na intake; high-Na intake suppressed renal renin content to a similar degree in KO and control. Plasma renin concentrations paralleled changes in renal renin content. Valsartan, an angiotensin receptor blocker (ARB), abolished the hypertension in CD ET-1 KO mice during normal Na intake. High-Na intake + ARB treatment increased blood pressure in CD ET-1 KO, but not in controls. High-Na intake was associated with reduced Na excretion in CD ET-1 KO animals, but no changes in water excretion or creatinine clearance were noted. Spironolactone, an aldosterone antagonist, also normalized blood pressure in CD ET-1 KO mice during normal Na intake, whereas high-Na intake + spironolactone raised blood pressure only in CD ET-1 KO animals. In summary, hypertension in CD ET-1 KO is partly due to angiotensin II and aldosterone. We speculate that CD-derived ET-1 may regulate, via a novel pathway, renal renin production.
肾集合管（CD）特异性敲除内皮素-1（ET-1）会导致高血压和钠排泄受损。先前的一项研究指出，这些敲除（KO）小鼠的肾素-血管紧张素-醛固酮轴未能被抑制，因此开展了当前的研究，以检查该系统在CD ET-1 KO中的作用。在正常钠摄入期间，CD ET-1 KO小鼠和对照小鼠肾脏中的肾素含量相似；高钠摄入使KO小鼠和对照小鼠的肾脏肾素含量受到相似程度的抑制。血浆肾素浓度与肾脏肾素含量的变化平行。缬沙坦，一种血管紧张素受体阻滞剂（ARB），在正常钠摄入期间消除了CD ET-1 KO小鼠的高血压。高钠摄入 + ARB治疗使CD ET-1 KO小鼠的血压升高，但对照小鼠未出现这种情况。高钠摄入与CD ET-1 KO动物的钠排泄减少有关，但未观察到水排泄或肌酐清除率的变化。醛固酮拮抗剂螺内酯在正常钠摄入期间也使CD ET-1 KO小鼠的血压恢复正常，而高钠摄入 + 螺内酯仅使CD ET-1 KO动物的血压升高。总之，CD ET-1 KO小鼠的高血压部分归因于血管紧张素II和醛固酮。我们推测，CD来源的ET-1可能通过一条新途径调节肾脏肾素的产生。
