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We continue our discussion of renal dose dopamine.
What are the experimentally proven renal effects of dopamine?

我们继续讨论肾脏剂量DA
何谓实验证明的DA的肾脏作用？（DA肾脏效应的机理）

参考答案：

尽管临床认为DA通过增加肾动脉血流而发挥保护肾脏的作用，但是相关数据一直不很明确。有大量研究表明，给与DA后肾血流增加和/或肾动脉阻力减少，但没有任何实验证明该结果与血压和心输出量无关。许多实验中并未报道血流动力学数据，而另外一些实验中，血压和/或心输出量的增加使得肾血流增加的结果解释更加复杂。

DA另外还有两种对肾脏的独立作用得到证实。第一为DA抑制肾小管球间反馈，虽然该作用只在老鼠中得到证实。第二为DA直接抑制近端肾小管细胞和髓质肾小管细胞部位的Na⁺/K⁺ ATP酶。其通过包含蛋白激酶C、蛋白激酶A、磷脂酶A₂和花生四烯酸的通路而发挥该作用。其净效应是液体摄取减少，这可能解释长期以来临床研究中发现的DA增加钠排出而不伴有GFR增加的现象。

Mayer Brezis[4]建立了复杂的动物模型，通过激光多普勒流量探针和氧微电极阐明了关于肾缺血的部位，同时检验了多巴胺的肾脏效应。结果发现，多巴胺增加肾血流但并不增加髓质的PO₂，这很可能是因为球管反馈（TGF）抑制的原因。如在以前的问题中提到，TGF是肾脏保护自身免受缺血损害的关键机制；使远端溶质减少是其主要的保护效应。多巴胺有一副作用为其对邻近肾小管溶质吸收的抑制，这也增加了溶质向髓质肾小管细胞输送。

What are the experimentally proven renal effects of dopamine?

Despite the prevailing clinical belief that dopamine preserves the kidney by increasing renal arterial blood flow, the data are equivocal. There are a number of studies which have shown increased renal blood flow and/or decreased renal artery resistance after dopamine administration, but none show an effect independent of blood pressure and cardiac output. In some studies the hemodynamic data are not reported, while in others the increases in blood pressure and/or cardiac output complicate interpretation of the resultant increase in renal blood flow.

There are two other independent effects of dopamine on the kidney which have been demonstrated quite clearly. The first is that dopamine inhibits the tubuloglomerular feedback response, although this has been shown only in rats. The second is that it directly inhibits the Na+/K+ ATPase on both proximal tubular cells and medullary tubular cells. This occurs via a pathway that involves protein kinase C, protein kinase A, phospholipase A2 and arachidonic acid metabolites. The net effect is a decrease in solute uptake which probably accounts for the consistent finding in clinical studies that dopamine increases sodium excretion without increasing GFR.

Mayer Brezis (4), whose sophisticated experimental model using laser Doppler flow probes and oxygen microelectrodes has elucidated the bulk of what is currently known about renal ischemia, examined the effects of dopamine on the kidney. He found that dopamine increased renal blood flow but did not improve medullary PO2. This finding is most likely due to the inhibition of tubulo-glomerular feedback (TGF). As mentioned in a previous question, the TGF response is the key mechanism by which the kidney defends itself against ischemia; decreased distal delivery of solute is the principal protective effect. There may an additional deleterious effect of dopamine's inhibition of proximal tubular solute uptake, as this also increases delivery of solute to the medullary tubular cells.

Question author: Andrew Friedrich, MD, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School

References:
1. Schnermann, J. et al. Effect of dopamine on the tubuloglomerular feedback mechanism. Am J Physiol 1990; 258:F790-798.
2. Seri, I. et al. Locally formed dopamine inhibits Na+/K+ ATPase activity in rat renal cortical tubular cells Am J Physiol1988; 255:F666-F673.
3. Satoh, T. et al. Different mechanisms of renal Na+/K+ ATPase regulation by protein kinases in proximal and distal nephron. Am J Physiol 1993; 265: F399-405.
4. Heyman SN, Kaminski N, Brezis M. Dopamine increases medullary blood flow without improving regional hypoxia. Exp Nephrol 1995; 3:33.
Site Editor: George Frendl, M.D., Ph.D.
Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Medical School


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