Nitric oxide synthase in macula densa regulates glomerular capillary pressure.
Nitric oxide synthase in macula densa regulates glomerular capillary pressure.
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DOI：
10.1073/pnas.89.24.11993
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发表时间：
1992-12
影响因子：
11.1
通讯作者：
C. Wilcox;W. Welch;F. Murad;S. Gross;Graham P. Taylor;R. Levi;H. Schmidt
中科院分区：
文献类型：
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作者：
C. Wilcox;W. Welch;F. Murad;S. Gross;Graham P. Taylor;R. Levi;H. Schmidt
肾小管液体被肾单位的特化细胞在Henle袢的升支和远曲小管的连接处（称为致密斑）重吸收，释放化合物，引起邻近的传入小动脉的血管收缩。这种小管肾小球反馈反应的激活降低了肾单位的肾小球毛细血管压力，因此降低了肾小球滤过率。肾小管-肾小球反馈反应以负反馈模式起作用，将肾小球毛细血管压力与肾小管-液体输送和重吸收联系起来。该系统与肾脏自身调节、肾素释放以及长期体液和血压稳态有关。在这里，我们报告说，精氨酸衍生的一氧化氮，在致密斑产生的，是一个额外的细胞间信号分子，在小管液体重吸收和计数器的传入小动脉的血管收缩过程中释放。抗大鼠小脑组成型一氧化氮合酶抗体特异性染色大鼠致密斑细胞。用N ω-甲基-L-精氨酸（一氧化氮合酶抑制剂）或绿脓菌素（一种脂溶性内皮源性舒张因子抑制剂）对单个肾单位致密斑段进行微灌注，结果表明一氧化氮的产生可使传入小动脉血管扩张，并增加肾小球毛细血管压;这种作用可被阻止肾小管液体重吸收的药物阻断。我们的结论是致密斑细胞中的一氧化氮合酶被激活的小管液体重吸收和介导的血管舒张成分的小管肾小球反馈反应。这些发现意味着，除了在内皮细胞调节血管张力和神经传递中的既定作用外，精氨酸衍生的一氧化氮在体液容量和血压稳态中的作用。
Tubular-fluid reabsorption by specialized cells of the nephron at the junction of the ascending limb of the loop of Henle and the distal convoluted tubule, termed the macula densa, releases compounds causing vasoconstriction of the adjacent afferent arteriole. Activation of this tubuloglomerular feedback response reduces glomerular capillary pressure of the nephron and, hence, the glomerular filtration rate. The tubuloglomerular feedback response functions in a negative-feedback mode to relate glomerular capillary pressure to tubular-fluid delivery and reabsorption. This system has been implicated in renal autoregulation, renin release, and longterm body fluid and blood-pressure homeostasis. Here we report that arginine-derived nitric oxide, generated in the macula densa, is an additional intercellular signaling molecule that is released during tubular-fluid reabsorption and counters the vasoconstriction of the afferent arteriole. Antibody to rat cerebellar constitutive nitric oxide synthase stained rat macula densa cells specifically. Microperfusion of the macula densa segment of single nephrons with N omega-methyl-L-arginine (an inhibitor of nitric oxide synthase) or with pyocyanin (a lipid-soluble inhibitor of endothelium-derived relaxation factor) showed that generation of nitric oxide can vasodilate the afferent arteriole and increase glomerular capillary pressure; this effect was blocked by drugs that prevent tubular-fluid reabsorption. We conclude that nitric oxide synthase in macula densa cells is activated by tubular-fluid reabsorption and mediates a vasodilating component to the tubuloglomerular feedback response. These findings imply a role for arginine-derived nitric oxide in body fluid-volume and blood-pressure homeostasis, in addition to its established roles in modulation of vascular tone by the endothelium and in neurotransmission.