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肾动脉上方严重主动脉束带对一氧化氮合酶同工型表达的影响。

Effect of severe aortic banding above the renal arteries on nitric oxide synthase isotype expression.

作者信息

Barton C H, Ni Z, Vaziri N D

机构信息

Division of Nephrology, University of California, Irvine, California, USA.

出版信息

Kidney Int. 2001 Feb;59(2):654-61. doi: 10.1046/j.1523-1755.2001.059002654.x.

Abstract

BACKGROUND

Severe aortic stenosis above the renal arteries leads to a reduction in renal perfusion, increased renin secretion, and elevation of arterial blood pressure above the stenotic site. Nitric oxide (NO) plays an important role in regulation of renal and systemic vascular resistance, renal blood flow, and Na(+) handling. Abdominal aortic banding provides an excellent model for simultaneous testing of the effects of increased and decreased pressure, flow, and shear stress in the same animal.

METHODS

We studied protein expressions of endothelial NO synthase (eNOS), inducible NOS (iNOS), and neuroneal NOS (nNOS) isotypes in the renal cortex, renal medulla, heart, brain, and aorta segments above and below the stenosis site three weeks after abdominal aortic banding above the renal arteries. The results were compared with those obtained in the sham-operated controls. NOS isotype proteins were measured by Western blot.

RESULTS

Compared with the control group, the banded group showed significant up-regulations of eNOS, iNOS, and nNOS in renal cortex and medulla. Likewise, heart eNOS, brain nNOS, and thoracic aorta eNOS proteins were significantly increased in the banded group. However, eNOS and iNOS expressions were unchanged in the aorta segment below the stenotic site. Likewise, iNOS expression in the heart and thoracic aorta remained unchanged in the banded animals. No significant difference was found in creatinine clearance or urinary protein excretion between the two groups.

CONCLUSIONS

These findings clearly demonstrate the up-regulatory action of increased pressure on eNOS expression in the thoracic aorta and heart and of nNOS expression in the brain. These data further show up-regulation of all NOS isotypes in the kidney, which must have helped to mitigate the associated hypoperfusion.

摘要

背景

肾动脉上方的严重主动脉狭窄会导致肾灌注减少、肾素分泌增加以及狭窄部位上方动脉血压升高。一氧化氮(NO)在调节肾和全身血管阻力、肾血流量以及钠(Na⁺)处理方面发挥着重要作用。腹主动脉缩窄为在同一动物中同时测试压力、流量和剪切应力增加及降低的影响提供了一个极佳模型。

方法

我们研究了肾动脉上方腹主动脉缩窄三周后,肾皮质、肾髓质、心脏、大脑以及狭窄部位上方和下方主动脉段中内皮型一氧化氮合酶(eNOS)、诱导型一氧化氮合酶(iNOS)和神经元型一氧化氮合酶(nNOS)亚型的蛋白表达。将结果与假手术对照组的结果进行比较。通过蛋白质印迹法测量一氧化氮合酶亚型蛋白。

结果

与对照组相比,缩窄组肾皮质和髓质中的eNOS、iNOS和nNOS显著上调。同样,缩窄组中心脏eNOS、大脑nNOS和胸主动脉eNOS蛋白显著增加。然而,狭窄部位下方主动脉段中的eNOS和iNOS表达未发生变化。同样,缩窄动物心脏和胸主动脉中的iNOS表达也保持不变。两组之间肌酐清除率或尿蛋白排泄无显著差异。

结论

这些发现清楚地证明了压力增加对胸主动脉和心脏中eNOS表达以及大脑中nNOS表达的上调作用。这些数据进一步表明肾脏中所有一氧化氮合酶亚型均上调,这必定有助于减轻相关的灌注不足。

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