Progression of glomerular filtration rate reduction determined in conscious Dahl salt-sensitive hypertensive rats.
Progression of glomerular filtration rate reduction determined in conscious Dahl salt-sensitive hypertensive rats.
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DOI：
10.1161/hypertensionaha.113.01194
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发表时间：
2013-07
期刊：
影响因子：
--
通讯作者：
Gretz N
中科院分区：
文献类型：
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作者：
Cowley AW Jr;Ryan RP;Kurth T;Skelton MM;Schock-Kusch D;Gretz N
用一种新的测量方法测定了清醒的Dahl盐敏感（SS）大鼠高血压形成过程中肾小球滤过率（GFR）的动态变化。利用小型化的装置，通过经皮激发和发射光通过皮肤的真实的时间检测来测量异硫氰酸荧光素（FITC）-左己内酯的消失曲线。对植入股静脉导管（染料注射和采样）和颈动脉导管（遥测平均动脉压（MAP））的大鼠进行了研究，同时维持0.4% NaCl饮食和转换为4.0%（HS）饮食后的第2、5、7、14和21天。另一组大鼠以0.4%维持21天作为时间对照。MAP从0.4%（130±2 mmHg）的最后一天开始逐渐升高，到HS的第5天达到显著性，到第21天平均为162±7 mmHg。SS大鼠HS第7天的尿白蛋白排泄量显著升高（3倍）。GFR在HS第14天从1.53±0.06 ml/min/100 g bwgt降至1.27±0.04。到第21天，GFR下降28%至1.1±0.04 ml/min/100 g bwgt（t1/2 28.4±1.1 min）。在整个研究中，未观察到HS引起的肌酐清除率（Ccre）显著降低，表明即使使用质谱法测量肌酐，Ccre测量也不敏感。我们的结论是，所观察到的GFR降低是高血压的结果，而不是原因，这种非侵入性的方法可以用于这些清醒的SS大鼠的肾功能的纵向评估。
Sequential changes in glomerular filtration rate (GFR) during development of hypertension in the conscious Dahl salt-sensitive (SS) rat were determined using a new method for measurement. Utilizing a miniaturized device, disappearance curves of fluorescein isothiocyanate (FITC)-sinistrin were measured by transcutaneous excitation and real time detection of the emitted light through the skin. Rats with implanted femoral venous catheters (dye injection and sampling) and carotid catheters (mean arterial pressure (MAP) by telemetry) were studied while maintained on a 0.4% NaCl diet and on days 2,5,7,14 and 21 after switching to 4.0% (HS) diet. A separate group of rats were maintained on 0.4% for 21 days as a time control. MAP rose progressively from the last day of 0.4% (130±2 mmHg) reaching significance by day 5 of HS and averaged 162±7 mmHg by day 21. Urine albumin excretion was significantly elevated (3×) by day 7 of HS in SS rats. GFR became reduced on day 14 of HS falling from 1.53±0.06 ml/min/100g bwgt to 1.27±0.04. By day 21, GFR had fallen 28% to 1.1±0.04 ml/min/100g bwgt (t1/2 28.4±1.1 min.) No significant reductions of creatinine clearance (Ccre) were observed throughout the study in response to HS demonstrating the insensitivity of Ccre measurements even with creatinine measured using mass spectrometry. We conclude that the observed reduction of GFR was a consequence and not a cause of the hypertension and that this non-invasive approach could be used in these conscious SS rats for a longitudinal assessment of renal function.