Buchwalow Igor B, Podzuweit Thomas, Bocker Werner, Samoilova Vera E, Thomas Sylvia, Wellner Maren, Baba Hideo A, Robenek Horst, Schnekenburger Jürgen, Lerch Markus M
Department of Medicine B, Westfälische Wilhelms-Universität Münster, D-48149 Münster, Germany.
FASEB J. 2002 Apr;16(6):500-8. doi: 10.1096/fj.01-0842com.
The concept of endothelium-derived relaxing factor (EDRF) put forward in 1980 by Furchgott and Zawadzki implies that nitric oxide (NO) produced by NO synthase (NOS) in the endothelium diffuses to the underlying vascular smooth muscle, where it modulates vascular tone as well as vascular smooth muscle cell (VSMC) proliferation by increasing cGMP formation with subsequent activation of cGMP-dependent protein kinase. According to this concept, VSMC do not express NOS by themselves. This attractive, simple scheme is now under considerable debate. To address this issue, we designed this study with the use of a novel supersensitive immunocytochemical technique of signal amplification with tyramide and electron microscopic immunogold labeling complemented with Western blotting, as in our recent studies demonstrating NOS in the myocardial and skeletal muscles. We provide the first evidence that, in contrast to the currently accepted view, VSMC in various blood vessels express all three NOS isoforms depending on the blood vessel type. These findings suggest an alternative mechanism by which local NOS expression may modulate vascular functions in an endothelium-independent manner.
1980年，弗奇戈特和扎瓦茨基提出的内皮衍生舒张因子（EDRF）概念表明，内皮细胞中一氧化氮合酶（NOS）产生的一氧化氮（NO）扩散到其下方的血管平滑肌，在那里它通过增加cGMP的形成以及随后激活cGMP依赖性蛋白激酶来调节血管张力和血管平滑肌细胞（VSMC）增殖。根据这一概念，VSMC自身不表达NOS。这个有吸引力的简单方案现在受到了相当大的争议。为了解决这个问题，我们设计了这项研究，采用了一种新的超灵敏免疫细胞化学技术，即酪胺信号放大技术和电子显微镜免疫金标记技术，并辅以蛋白质印迹法，就像我们最近在心肌和骨骼肌中证明存在NOS的研究一样。我们提供了首个证据，与目前公认的观点相反，不同血管中的VSMC根据血管类型表达所有三种NOS同工型。这些发现提示了一种替代机制，即局部NOS表达可能以内皮细胞非依赖的方式调节血管功能。
