Iodinated contrast induced renal vasoconstriction is due in part to the downregulation of renal cortical and medullary nitric oxide synthesis.
Iodinated contrast induced renal vasoconstriction is due in part to the downregulation of renal cortical and medullary nitric oxide synthesis.
复制标题
碘造影剂引起的肾血管收缩部分是由于肾皮质和髓质一氧化氮合成的下调所致。
DOI：
10.1016/j.jvs.2006.04.036
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发表时间：
2006
影响因子：
4.3
通讯作者：
Bartula,LoriL
中科院分区：
文献类型：
--
作者：
Myers,StuartI;Wang,Li;Liu,Fang;Bartula,LoriL
目的肾功能丧失仍然是用于诊断性血管造影和血管内手术的碘化造影剂的常见并发症。本研究检验了以下假设，即对比剂诱导的肾损伤部分是由于内源性肾皮质和髓质一氧化氮（NO）合成下调后皮质和髓质微血管血流量减少所致。将微透析探针或激光多普勒纤维插入肾皮质至2 mm的深度，并插入肾髓质至4 mm的深度。连续监测血流量，将微透析探针连接到注射泵，并以3 μL/min的乳酸林格氏溶液在体内灌注。在时间0（基础）和输注生理盐水或Conray 400（6 mL/kg）后60分钟收集透析液。两组均给予生理盐水载体、Nω-硝基-L-精氨酸甲酯盐酸盐（L-NAME，30 mg/kg）、L-精氨酸（400 mg/kg）或氧自由基清除剂超氧化物歧化酶（10，000 U/kg）。分析透析液的总NO和类二十烷酸合成。Western blot分析肾皮质和髓质中诱导型NO合酶（iNOS）、环氧合酶2（COX 2）、前列环素合酶和前列腺素E2（PGE 2）合酶的含量。此外，L-NAME的Conray进一步减少皮质和髓质血流量和NO的合成，这是恢复向控制L-精氨酸。L-NAME和L-精氨酸（添加到Conray中）都没有改变皮质或髓质类花生酸的释放。超氧化物歧化酶加入Conray处理后，髓质PGE 2合成减少，表明氧自由基在Conray处理后维持内源性髓质PGE 2合成方面具有保护作用。Conray没有显着改变iNOS、考克斯-2、前列环素合酶或PGE 2合酶的含量。结论这些发现表明肾皮质和髓质NO合成的下调导致了造影剂诱导的肾皮质和髓质微血管血流的损失。保持肾皮质和髓质NO合成的正常水平可能有助于预防或减轻造影剂诱导的肾血管收缩，并减轻诊断和治疗性血管内手术后发现的造影剂诱导的肾损伤。
OBJECTIVESThe loss of renal function continues to be a frequent complication of the iodinated contrast agents used to perform diagnostic angiography and endovascular procedures. This study examined the hypothesis that contrast-induced renal injury is partly due to a decrease in cortical and medullary microvascular blood flow after the downregulation of endogenous renal cortical and medullary nitric oxide (NO) synthesis.METHODSAnesthetized male Sprague-Dawley rats (300 g) had microdialysis probes or laser Doppler fibers inserted into the renal cortex to a depth of 2 mm and into the renal medulla to a depth of 4 mm. Laser Doppler blood flow was continuously monitored, and the microdialysis probes were connected to a syringe pump and perfused in vivo at 3 μL/min with lactated Ringer’s solution. Dialysate fluid was collected at time zero (basal) and 60 minutes after infusion of either saline or Conray 400 (6 mL/kg). Both groups were treated with saline carrier, Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME, 30 mg/kg), L-arginine (400 mg/kg), or superoxide dismutase (10,000 U/kg), an oxygen-derived free radical scavenger. Dialysate was analyzed for total NO and eicosanoid synthesis. The renal cortex and medulla were analyzed for inducible NO synthase (iNOS), cyclooxygenase-2 (COX2), prostacyclin synthase, and prostaglandin E2(PGE2) synthase content by Western blot analysis.RESULTSConray caused a marked decrease in cortical and medullary blood flow with a concomitant decrease in endogenous cortical NO, PGE2, and medullary NO synthesis. The addition of L-NAME to the Conray further decreased cortical and medullary blood flow and NO synthesis, which were restored toward control by L-arginine. Neither L-NAME nor L-arginine (added to the Conray) altered cortical or medullary eicosanoids release. Medullary PGE2synthesis decreased when superoxide dismutase was added to the Conray treatment, suggesting that oxygen-derived free radicals had a protective role in maintaining endogenous medullary PGE2synthesis after Conray treatment. Conray did not significantly alter iNOS, COX-2, prostacyclin synthase, or PGE2synthase content.CONCLUSIONSThese findings suggest that the downregulation of renal cortical and medullary NO synthesis contributes to the contrast-induced loss of renal cortical and medullary microvascular blood flow. Preservation of normal levels of renal cortical and medullary NO synthesis may help prevent or lessen contrast-induced renal vasoconstriction and lessen contrast-induced renal injury found after diagnostic and therapeutic endovascular procedures.