Song W, Abdel-Razik A E S, Lu W, Ao Z, Johns D G, Douglas S A, Balment R J, Ashton N
Faculty of Life Sciences, University of Manchester, Manchester, UK.
Kidney Int. 2006 Apr;69(8):1360-8. doi: 10.1038/sj.ki.5000290.
Urotensin II (UII) is a potent vasoactive hormone in mammals. However, despite its well-known effects on epithelial sodium transport in fish, little is known about its actions on the mammalian kidney. The aim of this study was to determine the effects of UII on renal function in the rat. Using standard clearance methods, the effects of rUII and the rat UII receptor (UT) antagonist, urantide, were studied. UII was measured in plasma and urine by radioimmunoassay. UII and UT were localized in the kidney by immunohistochemistry and mRNA expression quantified. Rat urinary [UII] was 1,650-fold higher than that in plasma. Immunoreactive-UII was localized to the proximal tubules, outer and inner medullary collecting ducts (IMCD); UT receptor was identified in glomerular arterioles, thin ascending limbs, and IMCD. UII and UT mRNA expression was greater in the medulla; expression was higher still in spontaneously hypertensive rats (SHRs) associated with raised plasma (UII). Injection of rUII induced reductions in glomerular filtration rate (GFR), urine flow, and sodium excretion. Urantide infusion resulted in increases in these variables. Endogenous UII appears to contribute to the regulation of GFR and renal sodium and water handling in the rat. While hemodynamic changes predominate, we cannot rule out the possibility of a direct tubular action of UII. Increased expression of UII and UT in the SHR suggests that UII plays a role in the pathophysiology of cardiovascular disease.
尾加压素II（UII）是哺乳动物体内一种强效的血管活性激素。然而，尽管其对鱼类上皮钠转运的作用已广为人知，但对其在哺乳动物肾脏中的作用却知之甚少。本研究的目的是确定UII对大鼠肾功能的影响。采用标准清除率方法，研究了重组UII（rUII）和大鼠UII受体（UT）拮抗剂尿抗利尿激素（urantide）的作用。通过放射免疫分析法测定血浆和尿液中的UII。采用免疫组织化学法对肾脏中的UII和UT进行定位，并对mRNA表达进行定量分析。大鼠尿中[UII]比血浆中高1650倍。免疫反应性UII定位于近端小管、外髓和内髓集合管（IMCD）；UT受体在肾小球小动脉、细升支和IMCD中被鉴定出来。UII和UT的mRNA表达在髓质中更高；在与血浆（UII）升高相关的自发性高血压大鼠（SHR）中表达更高。注射rUII导致肾小球滤过率（GFR）、尿流量和钠排泄减少。输注尿抗利尿激素导致这些变量增加。内源性UII似乎参与了大鼠GFR以及肾脏钠和水代谢的调节。虽然血流动力学变化占主导，但我们不能排除UII对肾小管有直接作用的可能性。SHR中UII和UT表达增加表明UII在心血管疾病的病理生理学中起作用。
