NITRIC-OXIDE AND PROSTANOIDS PROTECT THE RENAL OUTER MEDULLA FROM RADIOCONTRAST TOXICITY IN THE RAT
NITRIC-OXIDE AND PROSTANOIDS PROTECT THE RENAL OUTER MEDULLA FROM RADIOCONTRAST TOXICITY IN THE RAT
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DOI：
10.1172/jci117421
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发表时间：
1994-09-01
影响因子：
15.9
通讯作者：
BREZIS, M
中科院分区：
文献类型：
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作者：
AGMON, Y;PELEG, H;BREZIS, M
人体放射性造影剂肾毒性可通过多种风险因素的存在来预测，通常与肾循环受损相关。为了制备放射造影剂肾病的简单模型，在给予碘酞酸盐之前，用吲哚美辛和N ω-硝基-L-精氨酸甲酯（L-NAME，以抑制一氧化氮合成）预处理大鼠。持续发生急性肾衰竭，肌酐清除率从1.05+/-0.10降至0.27+/-0.05 ml/min（P < 0.001）与49+/-9%的髓质粗升支的选择性坏死有关。使用激光多普勒探头的血流动力学研究表明，当单独注射时，碘酞酸盐使外髓血流量增加至基线的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量，并将髓质血管扩张剂对放射性造影剂的反应转化为血管收缩，使髓质血流量延长至基线的一半以下。联合应用吲哚美辛、L-NAME和碘酞酸盐可使髓质血流量降至基线值的12 ± 4%.We得出结论，前列腺素类和一氧化氮在肾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的合成减少可能使患者易患放射造影剂肾病。
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.