Stanton B A, Kaissling B
Department of Physiology, Dartmouth Medical School, Hanover, New Hampshire 03756.
Am J Physiol. 1988 Dec;255(6 Pt 2):F1269-75. doi: 10.1152/ajprenal.1988.255.6.F1269.
This study was conducted to determine whether a chronic increase in sodium delivery to, and sodium uptake by, the distal tubule stimulates the transport capacity of this tubular segment. To increase the rate of sodium delivery to the distal tubule, furosemide (12 mg/day) was administered continuously to rats by osmotic minipump for 6 days. Volume depletion was prevented by giving the animals a drinking solution containing 0.8% NaCl and 0.1% KCl. Control animals were given vehicle (0.9% NaCl) by osmotic minipump and tap water to drink. All animals were adrenalectomized and given replacement doses of aldosterone (0.5 microgram.100 g-1.day-1) and dexamethasone (1.2 microgram.100 g-1.day-1) to eliminate changes in adrenal corticosteroid levels. Furosemide was withdrawn 12 h before sodium and potassium transport rates were measured in distal tubules by in vivo microperfusion. We found that increased sodium uptake dramatically enhanced the transport capacity of the distal tubule. Sodium absorption rose from 71.7 to 316.7 pmol.min-1.mm-1, and potassium secretion increased from 30.7 to 73.7 pmol.min-1.mm-1. This response was accompanied by an increase in cell and mitochondrial volume and by proliferation of the basolateral membrane of distal convoluted cells, connecting tubule cells, and principal cells in the distal tubule. We conclude that a chronic increase in sodium uptake by the distal tubule, independent of alterations in extracellular fluid volume and aldosterone levels, stimulates the transport capacity of this nephron segment in part by inducing specific alterations in cell ultrastructure.
本研究旨在确定远曲小管钠输送及钠摄取的慢性增加是否会刺激该肾小管节段的转运能力。为提高远曲小管的钠输送速率，通过渗透微型泵连续6天给大鼠注射呋塞米（12毫克/天）。通过给动物饮用含0.8%氯化钠和0.1%氯化钾的溶液来防止容量耗竭。对照动物通过渗透微型泵给予溶媒（0.9%氯化钠）并饮用自来水。所有动物均行肾上腺切除术，并给予替代剂量的醛固酮（0.5微克·100克⁻¹·天⁻¹）和地塞米松（1.2微克·100克⁻¹·天⁻¹）以消除肾上腺皮质激素水平的变化。在通过体内微灌注测量远曲小管钠和钾转运速率前12小时停用呋塞米。我们发现钠摄取增加显著增强了远曲小管的转运能力。钠吸收从71.7皮摩尔·分钟⁻¹·毫米⁻¹升至316.7皮摩尔·分钟⁻¹·毫米⁻¹，钾分泌从30.7皮摩尔·分钟⁻¹·毫米⁻¹增至73.7皮摩尔·分钟⁻¹·毫米⁻¹。这种反应伴随着细胞和线粒体体积的增加以及远曲小管中远端曲管细胞、连接小管细胞和主细胞基底外侧膜的增殖。我们得出结论，远曲小管钠摄取的慢性增加，独立于细胞外液容量和醛固酮水平的改变，部分通过诱导细胞超微结构的特定改变来刺激该肾单位节段的转运能力。
