Hypercholesterolemia aggravates radiocontrast nephrotoxicity: Protective role of L-arginine
Hypercholesterolemia aggravates radiocontrast nephrotoxicity: Protective role of L-arginine
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DOI：
10.1046/j.1523-1755.1998.00906.x
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发表时间：
1998-06-01
影响因子：
19.6
通讯作者：
Seguro, AC
中科院分区：
文献类型：
--
作者：
Andrade, L;Campos, SB;Seguro, AC
众所周知，放射性造影剂诱发的ARF依赖于与肾循环受损相关的危险因素。由于研究表明，高胆固醇血症（HC）患者内皮依赖性血管舒张功能受损，我们研究了放射性造影剂（RC）给药的影响（6 ml/kg体重，通过股动脉），在盐耗尽的大鼠中，保持正常胆固醇（NC）或HC饮食（4%胆固醇和1%胆酸）。放射造影剂给药后24小时，测量菊糖清除率（C-In，ml/min/100 g体重）、肾血流量（RBF;电磁流量计，ml/min/100 g体重）以及钠、钾和水（分别为FENa、FEK和FEH 2 O）、胆固醇（mg/dl）和白蛋白（g/dl）的排泄分数。与NC大鼠（RCNC）和对照大鼠相比，HC大鼠（RCHC）给予RC导致C-In值较低：0.36 +/- 0.085 vs 0.76 +/- 0.13 03（对照HC; P < 0.01），对比0.87 +/-0.06（对照NC; P < 0.01）。高胆固醇血症本身不改变肾功能，对照HC与对照NC相比不显著。与RCNC（4.3 +/- 0.3 vs. 6.1 +/- 0.3; P < 0.001）和对照动物（对照HC 8.2 +/- 0.3; P <0.001）以及对照NC 7.5 +/- 0.33（P < 0.001）相比，RCHC中的肾血液流量显著较低。为了研究一氧化氮（NO）的作用，HC大鼠在RC给药前以50 mg推注L-精氨酸或D-精氨酸（150 mg，经股动脉），其余剂量连续给药1小时。当与未处理的大鼠（RCHC）相比时，向RCHC大鼠施用L-精氨酸导致显著更高的C-In（0.86 +/- 0.1; P < 0.001）。D-精氨酸在C-In中未显示出显著差异（0.49 +/- 0.08）。D-精氨酸RCHC与L-精氨酸RCHC比较有显著性差异（P < 0.05）。在RCHC中，L-精氨酸可预防RBF下降（8.4 +/- 0.23 vs. 4.3 +/- 0.3; P < 0.001），但D-精氨酸不能预防RBF下降（5.1 +/- 0.57; Pt 0.001）。我们的数据表明，高胆固醇血症加重肾毒性，这是减弱L-精氨酸，但不是D-精氨酸管理，这表明一氧化氮在这种模型中起着重要的作用，急性肾功能衰竭。
It is well known that the radiocontrast-induced ARF depends on risk factors often associated with compromised renal circulation Since studies have shown that endothelium-dependent vasodilation is impaired in hypercholesterolemia (HC), we studied the effect of radiocontrast (RC) administration (6 ml/kg body wt, via femoral artery) in salt-depleted rats that were kept on a normal cholesterol (NC) or HC diet (4% cholesterol and 1% cholic acid). Inulin clearance (C-In, ml/min/100 g body wt), renal blood flow (RBF; electromagnetic flowmeter, ml/min/100 g body wt), and fractional excretions of sodium, potassium and water (FENa, FEK and FEH2O, respectively), cholesterol (mg/dl), and albumin (g/dl) were measured 24 hours after radiocontrast administration. The administration of RC to HC rats (RCHC) resulted in lower values of C-In compared with NC rats (RCNC) and control rats: 0.36 +/- 0.085 versus 0.76 +/- 0.13 (RCNC; P < 0.01), versus 0.84 +/- 0.03 (control HC; P < 0.01), versus 0.87 +/- 0.06 (control NC; P < 0.01). Hypercholesterolemia per se did not alter renal function, and control HC versus control NC was not significant. Renal blood how was significantly lower in the RCHC when compared to RCNC (4.3 +/- 0.3 vs. 6.1 +/- 0.3; P < 0.001) and to control animals (control HC 8.2 +/- 0.3; P < 0.001), and control NC 7.5 +/- 0.33 (P < 0.001). To study the role of nitric oxide (NO), HC rats were treated with an infusion of L-arginine or D-arginine (150 mg via femoral artery) in a 50 mg bolus before RC administration and the remaining dose continuously for a period of one hour. The administration of L-arginine to RCHC rats resulted in significantly higher C-In (0.86 +/- 0.1; P < 0.001) when compared to the untreated rats (RCHC). D-arginine did not show a significant difference in C-In (0.49 +/- 0.08). There was a considerable difference between D-arginine RCHC and L-arginine RCHC (P < 0.05). The RBF fall was prevented by L-arginine in RCHC (8.4 +/- 0.23 vs. 4.3 +/- 0.3; P < 0.001), but it was not prevented by D-arginine (5.1 +/- 0.57; Pt 0.001). Our data suggest that hypercholesterolemia aggravates nephrotoxicity, which is attenuated by L-arginine but not by D-arginine administration, suggesting that nitric oxide plays a significant role in this model of acute renal failure.