Ying W Z, Sanders P W
Nephrology Research and Training Center, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama 35294-0007, USA.
Am J Physiol. 1998 Jul;275(1):F18-24. doi: 10.1152/ajprenal.1998.275.1.F18.
Dietary salt controls production of nitric oxide (NO), a potent paracrine relaxation factor involved in glomerular filtration and salt excretion. We hypothesized that glomerular NO production was enhanced through endothelial nitric oxide synthase (NOS3). Rats in metabolic cages were studied after 4 days on 0.3% (Lo-salt) or 8.0% (Hi-salt) NaCl diet. Steady-state mRNA and protein levels of NOS3 and calcium-dependent NO production of isolated glomeruli from Hi-salt animals were greater than those values observed in glomeruli from Lo-salt rats. Because dietary salt enhanced glomerular production of transforming growth factor-beta1 (TGF-beta1) [W.-Z. Ying and P. W. Sanders. Am. J. Physiol. 274 (Renal Physiol. 43): F635-F641, 1998], studies were then conducted to examine the interaction between NOS3 and TGF-beta1. Glomerular steady-state levels of mRNA of NOS3 and TGF-beta1 directly correlated (r2 = 0. 946; P < 0.0001). A neutralizing antibody to TGF-beta reduced NOS3 protein and NO production in cultured glomeruli from Hi-salt animals to levels seen in the Lo-salt glomeruli. Thus dietary salt increased glomerular expression of TGF-beta1, which in turn augmented NO production through NOS3.
膳食盐可控制一氧化氮（NO）的生成，NO是一种强效旁分泌舒张因子，参与肾小球滤过和盐分排泄过程。我们推测肾小球NO的生成是通过内皮型一氧化氮合酶（NOS3）增强的。对处于代谢笼中的大鼠在0.3%（低盐）或8.0%（高盐）NaCl饮食条件下饲养4天后进行研究。高盐饮食组动物分离出的肾小球中，NOS3的稳态mRNA和蛋白质水平以及钙依赖性NO生成量均高于低盐饮食组大鼠肾小球中的相应值。由于膳食盐可增强转化生长因子-β1（TGF-β1）在肾小球中的生成[W.-Z. Ying和P. W. Sanders。《美国生理学杂志》274（肾脏生理学43）：F635 - F641，1998]，随后开展研究以检测NOS3与TGF-β1之间的相互作用。肾小球中NOS3和TGF-β1的mRNA稳态水平直接相关（r2 = 0.946；P < 0.0001）。针对TGF-β的中和抗体可将高盐饮食组动物培养的肾小球中NOS3蛋白水平和NO生成量降低至低盐饮食组肾小球中的水平。因此，膳食盐增加了TGF-β1在肾小球中的表达，进而通过NOS3增加了NO的生成。
