Suprarenal aortic clamping and reperfusion decreases medullary and cortical blood flow by decreased endogenous renal nitric oxide and PGE2 synthesis.
Suprarenal aortic clamping and reperfusion decreases medullary and cortical blood flow by decreased endogenous renal nitric oxide and PGE2 synthesis.
复制标题
肾上主动脉阻断和再灌注通过减少肾内源性一氧化氮和 PGE2 合成来减少髓质和皮质血流量。
DOI：
10.1016/j.jvs.2005.05.032
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发表时间：
2005
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：本研究探讨了将主动脉夹紧于肠系膜上动脉（SMA）上方，再进行肾上主动脉夹紧再灌注（SRACR）后，由于内源性髓质和皮质一氧化氮（NO）和前列腺素（PG） e2合成减少微血管血流的假设。研究设计麻醉的雄性spraguedawley大鼠（350 g）将微透析探针或激光多普勒纤维插入肾皮质2毫米深，并进入肾髓质4毫米。连续监测激光多普勒血流（数据以与基础相比的变化百分比报告），将微透析探针连接到注射泵上，以3 μL/min的速度在体内灌注乳酸林格液。在肾上主动脉夹持（缺血）30分钟后再灌注60分钟，并与假手术进行比较，在基础时间零点收集透析液。两组均给予生理盐水载体、吲哚美辛（INDO） （10 mg/kg，环氧化酶[COX]抑制剂）、ng -硝基-l-精氨酸甲酯（l-NAME） （20 mg/kg， NO合成酶[NOS]抑制剂）或l-精氨酸（200 mg/kg， NO前体）治疗。分析透析液总NO （μM）和PGE2（pg/mL）的合成。Western blot检测肾皮质和肾髓质诱导NOS （iNOS）和COX-2含量。所有数据以均数±SEM， N bbb50报告，方差分析。结果ssracr引起髓质和皮质血流明显减少，同时内源性髓质和皮质NO合成减少。l-NAME治疗进一步减少了髓质和皮质的血流量和NO合成。l-精氨酸恢复髓质和皮质NO合成和皮质血流量，但未恢复髓质血流量。SRACR未改变肾髓质或皮质PGE2；然而，添加INDO， COX抑制剂，引起髓质和皮质pge2合成和血流量的减少。结论sno是一种重要的内源性肾血管扩张剂，维持SRACR后可帮助维持肾皮质血流量。这些数据还表明，避免使用COX-2抑制剂可以帮助维持内源性肾皮质和髓质pge2合成，从而有助于维持正常的血流量。临床意义：该研究首次结合体内生理试验，同时鉴定维持微血管血流所需的具有临床意义的肾内血管扩张剂（皮质和髓质）。确定内源性肾皮质和髓质血管扩张剂负责维持肾微血管血流，将有助于制定治疗策略，以在SRACR后保留这些血管扩张剂。成功保留内源性肾内血管扩张剂将有助于维持肾微血管血流和肾功能，以治疗需要SRACR的复杂主动脉病变。
OBJECTIVEThis study examined the hypothesis that clamping the aorta above the superior mesenteric artery (SMA) followed by suprarenal aortic clamping and reperfusion (SRACR) decreases microvascular blood flow by loss of endogenous medullary and cortical nitric oxide (NO) and prostaglandin (PG) E2synthesis.STUDY DESIGNAnesthetized male Sprague-Dawley rats (350 g) had either microdialysis probes or laser Doppler fibers inserted into the renal cortex to a depth of 2 mm and into the renal medulla at 4 mm. Laser Doppler blood flow was continuously monitored (data reported as percentage of change compared to basal), and the microdialysis probes were connected to a syringe pump and perfused in vivo at 3 μL/min with lactated Ringer solution. Dialysate fluid was collected at basal time zero, following 30 minutes of suprarenal aortic clamping (ischemia) followed by 60 minutes of reperfusion and compared to a sham operation. Both groups were treated with saline carrier, indomethacin (INDO) (10 mg/kg, a cyclooxygenase [COX] inhibitor), NG-nitro-l-arginine methyl ester (l-NAME) (20 mg/kg, a NO synthase [NOS] inhibitor), or l-arginine (200 mg/kg, an NO precursor). Dialysate was analyzed for total NO (μM) and PGE2(pg/mL) synthesis. The renal cortex and medulla were analyzed for inducible NOS (iNOS) and COX-2 content by Western blot. All data are reported as mean ± SEM, N > 5 and analyzed by analysis of variance.RESULTSSRACR caused a marked decrease in medullary and cortical blood flow with a concomitant decrease in endogenous medullary and cortical NO synthesis. Treatment with l-NAME further decreased blood flow and NO synthesis in the medulla and cortex. l-Arginine restored medullary and cortical NO synthesis and blood flow in the cortex but not the medulla. SRACR did not alter renal medullary or cortical PGE2; however, addition of INDO, COX inhibitor, caused a concomitant decrease in medullary and cortical PGE2synthesis and blood flow.CONCLUSIONSNO is an important endogenous renal vasodilator that, when maintained can help preserve cortical blood flow following SRACR. These data also suggest that avoidance of COX-2 inhibitors can help maintain endogenous renal cortical and medullary PGE2synthesis and thus contribute to maintaining normal blood flow.CLINICAL RELEVANCEThis study is the first to combine in vivo physiologic assays to simultaneously identify clinically relevant intrarenal vasodilators (cortical and medullary) that are required to maintain microvascular blood flow. Identification of endogenous renal cortical and medullary vasodilators responsible for maintaining renal microvascular blood flow will allow development of treatment strategies to preserve these vasodilators following SRACR. Successful preservation of endogenous intrarenal vasodilators will help maintain renal microvascular blood flow and renal function in the treatment of complex aortic pathology that requires SRACR.