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Amendment history:
  • Correction (March 1998)

Research Article Free access | 10.1172/JCI119826

Importance of endothelium-derived hyperpolarizing factor in human arteries.

L Urakami-Harasawa, H Shimokawa, M Nakashima, K Egashira, and A Takeshita

Research Institute of Angiocardiology and Cardiovascular Clinic, Kyushu University School of Medicine, Fukuoka, Japan.

Find articles by Urakami-Harasawa, L. in: PubMed | Google Scholar

Research Institute of Angiocardiology and Cardiovascular Clinic, Kyushu University School of Medicine, Fukuoka, Japan.

Find articles by Shimokawa, H. in: PubMed | Google Scholar

Research Institute of Angiocardiology and Cardiovascular Clinic, Kyushu University School of Medicine, Fukuoka, Japan.

Find articles by Nakashima, M. in: PubMed | Google Scholar

Research Institute of Angiocardiology and Cardiovascular Clinic, Kyushu University School of Medicine, Fukuoka, Japan.

Find articles by Egashira, K. in: PubMed | Google Scholar

Research Institute of Angiocardiology and Cardiovascular Clinic, Kyushu University School of Medicine, Fukuoka, Japan.

Find articles by Takeshita, A. in: PubMed | Google Scholar

Published December 1, 1997 - More info

Published in Volume 100, Issue 11 on December 1, 1997
J Clin Invest. 1997;100(11):2793–2799. https://doi.org/10.1172/JCI119826.
© 1997 The American Society for Clinical Investigation
Published December 1, 1997 - Version history
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Abstract

The endothelium plays an important role in maintaining the vascular homeostasis by releasing vasodilator substances, including prostacyclin (PGI2), nitric oxide (NO), and endothelium-derived hyperpolarizing factor (EDHF). Although the former two substances have been investigated extensively, the importance of EDHF still remains unclear, especially in human arteries. Thus we tested our hypothesis that EDHF plays an important role in human arteries, particularly with reference to the effect of vessel size, its vasodilating mechanism, and the influences of risk factors for atherosclerosis. Isometric tension and membrane potentials were recorded in isolated human gastroepiploic arteries and distal microvessels (100-150 microm in diameter). The contribution of PGI2, NO, and EDHF to endothelium-dependent relaxations was analyzed by inhibitory effects of indomethacin, NG-nitro- L-arginine, and KCl, respectively. The nature of and hyperpolarizing mechanism by EDHF were examined by the inhibitory effects of inhibitors of cytochrome P450 pathway and of various K channels. The effects of atherosclerosis risk factors on EDHF-mediated relaxations were also analyzed. The results showed that (a) the contribution of EDHF to endothelium-dependent relaxations is significantly larger in microvessels than in large arteries; (b) the nature of EDHF may not be a product of cytochrome P450 pathway, while EDHF-induced hyperpolarization is partially mediated by calcium-activated K channels; and (c) aging and hypercholesterolemia significantly impair EDHF-mediated relaxations. These results demonstrate that EDHF also plays an important role in human arteries.

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