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The non-obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine
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- University of Muenster, Institute of Pathology, Muenster, Germany
- Institute of Normal and Pathological Physiology, Bratislava, Slovak Republic
- Institute for Pharmacology und Toxicology, Martin-Luther-University Halle-Wittenberg, Germany
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- Manuscript
- Date:
- Received 14 May 2008 11:25 UTC; Posted 14 May 2008
- Subjects:
- Molecular Cell Biology
- Abstract:
The concept of Endothelium Derived Relaxing Factor (EDRF), put forward by Furchgott in the earlier 80s of the past century, implies that nitric oxide (NO) produced by NO synthase (NOS) in the endothelium in response to acetylcholine (ACh) passively diffuses to the underlying vascular smooth muscle cells (VSMC) thereby reducing vascular tension. It was thought that VSMC do not express NOS by themselves, but to the time of those studies immunohistochemical techniques were not what they are now. State-of-the-art immunohistochemistry permits nowadays to localize NOS both to the endothelium and to VSMC. However, the principal question remained unanswered, is the NO generation by VSMC physiologically relevant? We hypothesized that the destruction of the vascular wall anatomical integrity by rubbing the blood vessel intimal surface may increase vascular superoxides that, in turn, reduce NO bioactivity. To address this issue, we examined ACh-induced vasorelaxation in endothelium-deprived blood vessels under protection against oxidative stress and found that superoxide scavengers – tempol and N-acetyl-L-cysteine – restored vasodilatory responses to ACh in endothelium-deprived blood vessels without influencing the vascular wall tension in intact blood vessels. Herewith we provided the first evidence that VSMC can release NO in amounts sufficient to account for the vasorelaxatory response to ACh. In contrast to the commonly accepted concept of the obligatory role of endothelial cells in the relaxation of arterial smooth muscle, the local NO generation by VSMC can modulate vascular functions in an endothelium-independent manner.
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- This document is licensed to the public under the Creative Commons Attribution 3.0 License
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Buchwalow, Igor, Cacanyiova, Sona, Neumann, Joachim, Samoilova, Vera, Boecker, Werner, and Kristek, Frantisek. The non-obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Available from Nature Precedings <http://hdl.handle.net/10101/npre.2008.1884.1> (2008)
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