Hus-Citharel Annette, Bouby Nadine, Frugière Alain, Bodineau Laurence, Gasc Jean-Marie, Llorens-Cortes Catherine
INSERM, U 691, Paris, France.
Kidney Int. 2008 Aug;74(4):486-94. doi: 10.1038/ki.2008.199. Epub 2008 May 28.
Apelin is a vasoactive peptide identified as the endogenous ligand of an orphan G protein-coupled receptor called APJ. Apelin and its receptor have been found in the brain and the cardiovascular system. Here we show that the apelin receptor mRNA is highly expressed in the glomeruli while its level of expression is lower in all nephron segments including collecting ducts that express vasopressin V2 receptors. Intravenous injection of apelin 17 into lactating rats induced a significant diuresis. Apelin receptor mRNA was also found in endothelial and vascular smooth muscle cells of glomerular arterioles. Apelin administration caused vasorelaxation of angiotensin II-preconstricted efferent and afferent arterioles as shown by an increase in their diameter. Activation of endothelial apelin receptors caused release of nitric oxide which inhibited angiotensin II-induced rise in intracellular calcium. In addition, it appears that apelin had a direct receptor-mediated vasoconstrictive effect on vascular smooth muscle. These results show that apelin has complex effects on the pre- and post glomerular microvasculature regulating renal hemodynamics. Its role on tubular function (if any) remains to be determined.
阿片肽是一种血管活性肽,被鉴定为一种名为APJ的孤儿G蛋白偶联受体的内源性配体。阿片肽及其受体已在大脑和心血管系统中被发现。在此我们表明,阿片肽受体mRNA在肾小球中高度表达,而在包括表达血管加压素V2受体的集合管在内的所有肾单位节段中其表达水平较低。给哺乳期大鼠静脉注射阿片肽17可诱导显著的利尿作用。在肾小球小动脉的内皮细胞和血管平滑肌细胞中也发现了阿片肽受体mRNA。如阿片肽给药导致血管紧张素II预收缩的出球小动脉和入球小动脉舒张,表现为其直径增加。内皮阿片肽受体的激活导致一氧化氮释放,抑制血管紧张素II诱导的细胞内钙升高。此外,阿片肽似乎对血管平滑肌有直接的受体介导的血管收缩作用。这些结果表明,阿片肽对肾小球前和肾小球后微血管系统有复杂作用,调节肾血流动力学。其对肾小管功能的作用(如果有的话)仍有待确定。