Renal dopamine system - Paracrine regulator of sodium homeostasis and blood pressure
Renal dopamine system - Paracrine regulator of sodium homeostasis and blood pressure
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DOI：
10.1161/hy0901.096422
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发表时间：
2001-09-01
期刊：
影响因子：
8.3
通讯作者：
Carey, RM
中科院分区：
文献类型：
--
作者：
Carey, RM
一个完整的多巴胺系统的所有组成部分都存在于肾脏内，其中多巴胺作为旁分泌物质控制钠的排泄。多巴胺受体可分为刺激腺苷酸环化酶的D-1样（D-1和D-5）受体和抑制腺苷酸环化酶的D-2样（D-2、D-3和D-4）受体。所有5种受体亚型都在肾脏中表达，尽管拷贝数较低。多巴胺在近端小管细胞中神经元合成，从这些细胞大量输出到小管腔，并与D-1样受体相互作用以抑制Na+-H+交换器和Na+，K+-ATP酶，减少小管钠重吸收。在中度钠过量期间，D-1样受体的多巴胺张力约占钠排泄的50%。在实验性高血压和人类高血压中，已经描述了2种肾脏多巴胺能缺陷：（1）肾脏多巴胺生成减少和（2）D-1受体-G蛋白偶联缺陷。这两种缺陷导致肾钠潴留，并且每一种都可能在原发性高血压的病理生理学中起重要作用。
All of the components of a complete dopamine system are present within the kidney, where dopamine acts as a paracrine substance in the control of sodium excretion. Dopamine receptors can be divided into D-1-like (D-1 and D-5) receptors that stimulate adenylyl cyclase and D-2-like (D-2, D-3, and D-4) receptors that inhibit adenylyl cyclase. All 5 receptor subtypes are expressed in the kidney, albeit in low copy. Dopamine is synthesized extraneuronally in proximal tubule cells, exported from these cells largely into the tubule lumen, and interacts with D-1-like receptors to inhibit the Na+-H+ exchanger and Na+,K+-ATPase, decreasing tubule sodium reabsorption. During moderate sodium surfeit, dopamine tone at D-1-like receptors accounts for approximate to 50% of sodium excretion. In experimental and human hypertension, 2 renal dopaminergic defects have been described: (1) decreased renal generation of dopamine and (2) a D-1 receptor-G protein coupling defect. Both defects lead to renal sodium retention, and each may play an important role in the pathophysiology of essential hypertension.