Rapid, dynamic changes in glomerular permeability to macromolecules during systemic angiotensin II (ANG II) infusion in rats
Rapid, dynamic changes in glomerular permeability to macromolecules during systemic angiotensin II (ANG II) infusion in rats
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DOI：
10.1152/ajprenal.00153.2012
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发表时间：
2012-09-01
影响因子：
4.2
通讯作者：
Rippe, Bengt
中科院分区：
文献类型：
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作者：
Axelsson, Josefin;Rippe, Anna;Rippe, Bengt
杨志华，李志华，B志华.大鼠全身血管紧张素II（ANG II）输注期间肾小球对大分子通透性的快速动态变化。Am J Physiol Renal Physiol 303：F790-F799，2012年。首次发表于2012年6月20日; doi：10.1152/ajprenal.00153.2012.-在体内研究了全身血管紧张素II（ANG II）输注对肾小球通透性的作用。在麻醉的Wistar大鼠（250-280 g）中，将左输尿管插管用于尿液收集，同时实现血液通路。大鼠连续静脉输注四种剂量的ANG II中的任一种，范围从16 ng.kg g·kg（-1）·min（-1）（Lo-ANG II）到1.82 μ g·kg（-1）·min（-1）（Hi-ANG II），并在单独的实验中用醛固酮（Aldo; 0.22 mg.kg（-1）. min（-1）），或与钙通道阻断剂尼莫地平，或与Aldo拮抗剂螺内酯以及高ANGII剂量（910 ng.kg（-1）.min（-1）; Hi-Int-ANGII），以及与多分散FITC-Ficoll-70/400（分子半径10-80埃）和Cr-51-EDTA。在5、15、30、60和120 min时采集血浆和尿液样品，并通过高效分子排阻色谱法进行分析，以测定肾小球对Ficoll的筛分系数（θ）。还评估了平均动脉压（MAP）和肾小球滤过率（GFR）。对于ANG II，Ficoll分子半径>34埃时肾小球通透性（θ）快速、显著、部分可逆增加，在5-15分钟达到峰值，ANG II阻滞剂坎地沙坦可完全消除该增加，但在15和30分钟时螺内酯未对其产生影响。对于Aldo，该反应与输注最低剂量ANG II时的反应相似。对于给予的两种最高ANG II剂量（Hi-Int-ANG II和Hi-ANG II），GFR一过性降低，同时MAP显著持续升高。尼莫地平完全阻断所有的血流动力学ANG II的行动，而肾小球通透性反应保持不变。因此，血管紧张素II直接增加肾小球通透性独立于其血流动力学的作用，并在很大程度上独立于伴随的阿尔多反应。ANG II诱导的肾小球通透性增加，根据双孔和对数正态分布孔模型，与肾小球过滤器中“大孔”数量增加相容，并且在一定程度上增加了小孔半径的分散性。
Axelsson J, Rippe A, Oberg CM, Rippe B. Rapid, dynamic changes in glomerular permeability to macromolecules during systemic angiotensin II (ANG II) infusion in rats. Am J Physiol Renal Physiol 303: F790-F799, 2012. First published June 20, 2012; doi: 10.1152/ajprenal.00153.2012.-The actions of systemic angiotensin II (ANG II) infusions on glomerular permeability were investigated in vivo. In anesthetized Wistar rats (250-280 g), the left ureter was cannulated for urine collection, while simultaneously blood access was achieved. Rats were continuously infused intravenously with either of four doses of ANG II ranging from 16 ng.kg(-1).min(-1) (Lo-ANG II) to 1.82 mu g.kg(-1).min(-1) (Hi-ANG II), and in separate experiments with aldosterone (Aldo; 0.22 mg.kg(-1.)min(-1)), or with the calcium channel blocker nimodipine, or with the Aldo antagonist spironolactone together with a high ANGII dose (910 ng.kg(-1).min(-1); Hi-Int-ANG II), respectively, and with polydisperse FITC-Ficoll-70/400 (molecular radius 10-80 angstrom) and Cr-51-EDTA. Plasma and urine samples were taken at 5, 15, 30, 60, and 120 min and analyzed by high performance size-exclusion chromatography for determination of glomerular sieving coefficients (theta) to Ficoll. Mean arterial pressure (MAP) and glomerular filtration rate (GFR) were also assessed. For ANG II, there was a rapid, marked, partly reversible increase in glomerular permeability (theta) for Ficoll molecules >34 angstrom in radius, peaking at 5-15 min, which was completely abrogated by the ANG II blocker candesartan but not affected by spironolactone at 15 and 30 min. For Aldo, the response was similar to that found for the lowest dose of ANG II infused. For the two highest ANG II doses given (Hi-Int-ANG II and Hi-ANG II), GFR decreased transiently, concomitant with marked, sustained increases in MAP. Nimodipine completely blocked all hemodynamic ANG II actions, whereas the glomerular permeability response remained unchanged. Thus ANG II directly increased glomerular permeability independently of its hemodynamic actions and largely independently of the concomitant Aldo response. The ANG II-induced increases in glomerular permeability were, according to a two-pore and a log-normal distributed pore model, compatible with an increased number of "large pores" in the glomerular filter, and, to some extent, an increase in the dispersity of the small-pore radius.