Agmon Y, Peleg H, Greenfeld Z, Rosen S, Brezis M
Department of Medicine, Hadassah University Hospital, Mount-Scopus, Jerusalem, Israel.
J Clin Invest. 1994 Sep;94(3):1069-75. doi: 10.1172/JCI117421.
Human radiocontrast nephrotoxicity is predicted by the presence of multiple risk factors, often associated with compromised renal circulation. To produce a simple model of radiocontrast nephropathy, rats were pretreated with indomethacin and N omega-nitro-L-arginine methyl ester (L-NAME, to inhibit nitric oxide synthesis) before the administration of iothalamate. Acute renal failure consistently developed, with a decline in creatinine clearance from 1.05 +/- 0.10 to 0.27 +/- 0.05 ml/min (P < 0.001) associated with selective necrosis of 49 +/- 9% of medullary thick ascending limbs. Hemodynamic studies using laser-Doppler probes revealed that when injected alone, iothalamate increased outer medullary blood flow to 196 +/- 25% of baseline (P < 0.001). Pretreatment by L-NAME or indomethacin both reduced basal medullary blood flow and transformed the medullary vasodilator response to radiocontrast into vasoconstriction, with a prolonged reduction of medullary blood flow to less then half of baseline. Combined administration of indomethacin, L-NAME, and iothalamate lowered medullary blood flow to 12 +/- 4% of baseline. We conclude that prostanoids and nitric oxide have an important protective role in the renal response to radiocontrast material. Reduced synthesis of these vasoactive substances in renal/vascular diseases may predispose patients to radiocontrast nephropathy.
多种风险因素的存在可预测人类放射性造影剂肾毒性，这些因素常与肾循环受损有关。为建立一个简单的放射性造影剂肾病模型，在给予碘他拉酸盐之前，先用吲哚美辛和N-ω-硝基-L-精氨酸甲酯（L-NAME，抑制一氧化氮合成）对大鼠进行预处理。持续出现急性肾衰竭，肌酐清除率从1.05±0.10降至0.27±0.05 ml/分钟（P<0.001），同时49±9%的髓袢升支粗段出现选择性坏死。使用激光多普勒探头进行的血流动力学研究显示，单独注射碘他拉酸盐时，可使髓质外层血流增加至基线的196±25%（P<0.001）。L-NAME或吲哚美辛预处理均降低了基础髓质血流，并将髓质对放射性造影剂的血管舒张反应转变为血管收缩，髓质血流持续减少至基线的一半以下。联合给予吲哚美辛、L-NAME和碘他拉酸盐可使髓质血流降至基线的12±4%。我们得出结论，前列腺素和一氧化氮在肾脏对放射性造影剂的反应中具有重要的保护作用。肾/血管疾病中这些血管活性物质合成减少可能使患者易患放射性造影剂肾病。
