Department of Physiology and Hypertension and Renal Center of Excellence, Tulane University Health Sciences Center School of Medicine, New Orleans, Louisiana 70112, USA.
Am J Physiol Renal Physiol. 2010 Jan;298(1):F103-8. doi: 10.1152/ajprenal.00479.2009. Epub 2009 Nov 11.
Atrial natriuretic peptide (ANP) elicits natriuresis; however, the relative contributions of proximal and distal nephron segments to the overall ANP-induced natriuresis have remained uncertain. This study was performed to characterize the effects of ANP on distal nephron sodium reabsorption determined after blockade of the two major distal nephron sodium transporters with amiloride (5 microg/g body wt) plus bendroflumethiazide (12 microg/g body wt) in male anesthetized C57/BL6 and natriuretic peptide receptor-A gene (Npr1) targeted four-copy mice. The lower dose of ANP (0.1 ng x g body wt(-1) x min(-1), n = 6) increased distal sodium delivery (DSD, 2.4 +/- 0.4 vs. 1.6 +/- 0.2 mueq/min, P < 0.05) but did not change fractional reabsorption of DSD compared with control (86.3 +/- 2.0 vs. 83.9 +/- 3.6%, P > 0.05), thus limiting the magnitude of the natriuresis. In contrast, the higher dose (0.2 ng x g body wt(-1) x min(-1), n = 6) increased DSD (2.8 +/- 0.3 mueq/min, P < 0.01) and also decreased fractional reabsorption of DSD (67.4 +/- 4.5%, P < 0.01), which markedly augmented the natriuresis. In Npr1 gene-duplicated four-copy mice (n = 6), the lower dose of ANP increased urinary sodium excretion (0.6 +/- 0.1 vs. 0.3 +/- 0.1 mueq/min, P < 0.05) and decreased fractional reabsorption of DSD compared with control (72.2 +/- 3.4%, P < 0.05) at similar mean arterial pressures (91 +/- 6 vs. 92 +/- 3 mmHg, P > 0.05). These results provide in vivo evidence that ANP-mediated increases in DSD alone exert modest effects on sodium excretion and that inhibition of fractional reabsorption of distal sodium delivery is requisite for the augmented natriuresis in response to the higher dose of ANP or in Npr1 gene-duplicated mice.
心房利钠肽（ANP）可引起钠排泄；然而，近端和远端肾单位在整体 ANP 诱导的钠排泄中的相对贡献仍不确定。本研究旨在描述在使用阿米洛利（5 µg/g 体重）加布美他尼（12 µg/g 体重）阻断两种主要的远端肾单位钠转运体后，ANP 对远端肾单位钠重吸收的影响，该研究在雄性麻醉 C57/BL6 小鼠和利钠肽受体-A 基因（Npr1）靶向四拷贝小鼠中进行。较低剂量的 ANP（0.1 ng·g 体重-1·min-1，n=6）增加了远端钠输送（DSD，2.4±0.4 比 1.6±0.2 μeq/min，P＜0.05），但与对照组相比，并未改变 DSD 的分数重吸收（86.3±2.0 比 83.9±3.6%，P＞0.05），从而限制了钠排泄的幅度。相比之下，较高剂量（0.2 ng·g 体重-1·min-1，n=6）增加了 DSD（2.8±0.3 μeq/min，P＜0.01），并降低了 DSD 的分数重吸收（67.4±4.5%，P＜0.01），这显著增强了钠排泄。在 Npr1 基因四拷贝小鼠中（n=6），较低剂量的 ANP 增加了尿钠排泄（0.6±0.1 比 0.3±0.1 μeq/min，P＜0.05），并降低了 DSD 的分数重吸收（72.2±3.4%，P＜0.05），与对照组相比，平均动脉压相似（91±6 比 92±3 mmHg，P＞0.05）。这些结果提供了体内证据，表明 ANP 介导的 DSD 增加单独对钠排泄产生适度影响，并且抑制远端钠输送的分数重吸收是对较高剂量 ANP 或 Npr1 基因四拷贝小鼠的增强钠排泄反应所必需的。
