Wilcox C S
Georgetown University Medical Center, Washington, DC, USA.
Curr Opin Nephrol Hypertens. 1998 Jul;7(4):443-9. doi: 10.1097/00041552-199807000-00016.
Recent studies have amply confirmed the robust expression of neuronal nitric oxide synthase (nNOS) in macula densa cells and its function in blunting tubuloglomerular feedback responses. Regulation of nNOS may occur at many levels: (1) transcriptional and translational regulation, which is enhanced by salt restriction and angiotensin II; (2) functional enhancement by L-arginine delivery and uptake via system Y+, which is enhanced during salt loading; (3) structural activation and feedback inhibition provided by postsynaptic density proteins co-expressed with nNOS in the macula densa; (4) competitive inhibition by dimethylarginines, which can be metabolized via NG, NG dimethylarginine dimethylaminohydrolase co-expressed with nNOS in the macula densa; and (5) intracellular activation linked to changes in [Ca++] or pH during luminal Na+ reabsorption. Nitric oxide, once formed, can be degraded by O2- produced principally in the interstitium between the macula densa and afferent arteriole and in the wall of the arteriole. In genetic hypertension, tubuloglomerular feedback responses are enhanced, in part at least because of diminished buffering by macula densa NO and enhanced O2- generation in the juxtaglomerular apparatus. These recent studies highlight the importance of the macula densa nitric oxide-tubuloglomerular feedback system in adapting glomerular hemodynamics and renal function to changes in salt intake, and define potentially important defects in models of genetic hypertension.
最近的研究充分证实了神经元型一氧化氮合酶（nNOS）在致密斑细胞中的强烈表达及其在减弱肾小管-肾小球反馈反应中的作用。nNOS的调节可能发生在多个层面：（1）转录和翻译调节，盐限制和血管紧张素II可增强这种调节；（2）通过系统Y+进行L-精氨酸的递送和摄取实现功能增强，在盐负荷增加时这种增强作用更为明显；（3）致密斑中与nNOS共表达的突触后致密蛋白提供结构激活和反馈抑制；（4）二甲基精氨酸的竞争性抑制，其可通过致密斑中与nNOS共表达的NG，NG-二甲基精氨酸二甲胺水解酶进行代谢；（5）管腔钠重吸收过程中与[Ca++]或pH变化相关的细胞内激活。一氧化氮一旦形成，可被主要在致密斑和入球小动脉之间的间质以及小动脉壁中产生的超氧阴离子降解。在遗传性高血压中，肾小管-肾小球反馈反应增强，至少部分原因是致密斑一氧化氮的缓冲作用减弱以及肾小球旁器中超氧阴离子生成增加。这些最新研究突出了致密斑一氧化氮-肾小管-肾小球反馈系统在使肾小球血流动力学和肾功能适应盐摄入变化方面的重要性，并确定了遗传性高血压模型中潜在的重要缺陷。
