Important role of endothelium-derived hyperpolarizing factor in shear stress-induced endothelium-dependent relaxations in the rat mesenteric artery

Yoshiaki Takamura, Hiroaki Shimokawa, Huiying Zhao, Hirohito Igarashi, Kensuke Egashira, Akira Takeshita

    Research output: Contribution to journalArticlepeer-review

    62 Citations (Scopus)

    Abstract

    Shear stress is one of the most important stimulators for the release of endothelium-derived relaxing factors. Although shear stress-induced release of nitric oxide (NO) has been extensively investigated, it remains to be elucidated whether endothelium-derived hyperpolarizing factor (EDHF) contributes to the endothelium-dependent relaxations to shear stress. This study was designed to address this point in the isolated rat mesenteric artery. Large mesenteric arteries (400500 μm)and resistance mesenteric arteries (150-250 μm) of the rat were precontracted with phenylephrine (at 80 mm Hg of perfusion pressure), and the changes in vessel diameter in response to variable flow (0-300 μl/min) were continuously examined. The relative contributions of vasodilator prostaglandins, NO, and EDHF were analyzed by the inhibitory effects of indomethacin (10-5 M), N(G)-nitro-L- arginine (L-NNA, 10-4 M), and KCl (40 mM), respectively. The shear stress- induced relaxations were totally endothelium dependent in both-sized blood vessels, and the contribution of NO was more prominent in large arteries than in resistance arteries, whereas that of EDHF was noted in both-sized blood vessels. Tetrabutylammonium (a nonselective inhibitor of K channels) almost abolished, whereas the combination of charybdotoxin (an inhibitor of both large- and intermediate-conductance Ca2+-activated K channels) and apamin (an inhibitor of small-conductance Ca2+-activated K channels) significantly inhibited the EDHF-mediated component of the shear stress-induced relaxations. These results indicate that EDHF plays an important role in shear stress-induced endothelium-dependent relaxations, where K channels, especially calcium-activated K channels, appear to be involved.

    Original languageEnglish
    Pages (from-to)381-387
    Number of pages7
    JournalJournal of Cardiovascular Pharmacology
    Volume34
    Issue number3
    DOIs
    Publication statusPublished - Sep 1999

    All Science Journal Classification (ASJC) codes

    • Pharmacology
    • Cardiology and Cardiovascular Medicine

    Fingerprint

    Dive into the research topics of 'Important role of endothelium-derived hyperpolarizing factor in shear stress-induced endothelium-dependent relaxations in the rat mesenteric artery'. Together they form a unique fingerprint.

    Cite this