Markewitz B A, Michael J R, Kohan D E
Department of Medicine, Veterans Administration Medical Center, Salt Lake City, Utah.
J Clin Invest. 1993 May;91(5):2138-43. doi: 10.1172/JCI116439.
Nitric oxide (NO.) has been implicated in the regulation of renal vascular tone and tubular sodium transport. While the endothelial cell is a well known source of NO(.), recent studies suggest that tubular epithelial cells may constitutively generate NO(.). An inducible isoform of nitric oxide synthase which produces far greater quantities of NO. exists in some cell types. We sought to determine whether kidney epithelial cells exposed to cytokines could express an inducible nitric oxide synthase. Primary cultures of rat proximal tubule and inner medullary collecting duct cells generated NO. on exposure to TNF-alpha and IFN-gamma. NO. production by both cell types was inhibited by NG-monomethyl-L-arginine; this inhibition was partially reversed by the addition of excess L-arginine. Stimulation of kidney epithelial cells with TNF-alpha and IFN-gamma dramatically increased the level of inducible nitric oxide synthase mRNA. In summary, renal proximal tubule and inner medullary collecting duct cells can produce NO. via expression of an inducible isoform of nitric oxide synthase.
一氧化氮（NO.）与肾血管张力调节及肾小管钠转运有关。虽然内皮细胞是众所周知的NO（.）来源，但最近的研究表明，肾小管上皮细胞可能会持续产生NO（.）。在某些细胞类型中存在一种可诱导的一氧化氮合酶同工型，其产生的NO.量要多得多。我们试图确定暴露于细胞因子的肾上皮细胞是否能表达可诱导的一氧化氮合酶。大鼠近端小管和髓质内集合管细胞的原代培养物在暴露于肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ）时会产生NO.。两种细胞类型产生的NO.均被NG-单甲基-L-精氨酸抑制；添加过量的L-精氨酸可部分逆转这种抑制作用。用TNF-α和IFN-γ刺激肾上皮细胞可显著增加可诱导的一氧化氮合酶mRNA水平。总之，肾近端小管和髓质内集合管细胞可通过表达可诱导的一氧化氮合酶同工型产生NO.。
