PAH clearance after renal ischemia and reperfusion is a function of impaired expression of basolateral Oat1 and Oat3.
PAH clearance after renal ischemia and reperfusion is a function of impaired expression of basolateral Oat1 and Oat3.
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DOI：
10.1002/phy2.243
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发表时间：
2014-02-01
影响因子：
2.5
通讯作者：
Sauvant, Christoph
中科院分区：
文献类型：
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作者：
Bischoff, Ariane;Bucher, Michael;Gekle, Michael;Sauvant, Christoph
通过对氨基马尿酸 (PAH) 清除率测定肾血浆流量 (RPF) 会导致对相应参数的严重低估，因为肾缺血和再灌注损伤后肾对 PAH 的提取受损。然而，对于这种现象还没有机械解释。根据我们之前的研究，我们假设这可能是由于基底外侧限速有机阴离子转运蛋白 Oat1 和 Oat3 的表达受损所致。因此，我们通过测定 PAH 清除率、PAH 提取率、PAH 净分泌率以及 rOat1 和 rOat3 的表达，在肾缺血和再灌注大鼠模型中研究了这一现象。缺血和再灌注后 PAH 提取严重受损，如果不考虑 PAH 提取率，则导致 RPF 被低估三倍。 PAH 提取与基底外侧 Oat1 和 Oat3 的表达直接相关。肾小管 PAH 分泌与 PAH 提取直接相关。因此，我们的数据通过降低限速基底外侧有机阴离子转运蛋白 Oat1 和 Oat3 的表达来解释肾 PAH 提取受损。此外，我们表明，PAH 净分泌量的测定适用于纠正缺血和再灌注后提取受损的 PAH 清除率，以便获得 RPF 的有效结果。由于肾缺血和再灌注损伤后肾对 PAH 的提取受损，通过 PAH 清除率确定肾血浆流量会导致对相应参数的严重低估。然而，到目前为止，还没有对这种现象的机械解释。因此，我们的数据通过降低限速基底外侧有机阴离子转运蛋白 Oat1 和 Oat3 的表达来解释肾 PAH 提取受损。
Determination of renal plasma flow (RPF) by para‐aminohippurate (PAH) clearance leads to gross underestimation of this respective parameter due to impaired renal extraction of PAH after renal ischemia and reperfusion injury. However, no mechanistic explanation for this phenomenon is available. Based on our own previous studies we hypothesized that this may be due to impairment of expression of the basolateral rate limiting organic anion transporters Oat1 and Oat3. Thus, we investigated this phenomenon in a rat model of renal ischemia and reperfusion by determining PAH clearance, PAH extraction, PAH net secretion, and the expression of rOat1 and rOat3. PAH extraction was seriously impaired after ischemia and reperfusion which led to a threefold underestimation of RPF when PAH extraction ratio was not considered. PAH extraction directly correlated with the expression of basolateral Oat1 and Oat3. Tubular PAH secretion directly correlated with PAH extraction. Consequently, our data offer an explanation for impaired renal PAH extraction by reduced expression of the rate limiting basolateral organic anion transporters Oat1 and Oat3. Moreover, we show that determination of PAH net secretion is suitable to correct PAH clearance for impaired extraction after ischemia and reperfusion in order to get valid results for RPF. Determination of renal plasma flow by PAH clearance leads to gross underestimation of this respective parameter due to impaired renal extraction of PAH after renal ischemia and reperfusion injury. However, no mechanistic explanation for this phenomenon was available up to now. Consequently, our data offer an explanation for impaired renal PAH extraction by reduced expression of the rate limiting basolateral organic anion transporters Oat1 and Oat3.