Involvement of endothelin in the regulation of human vascular tonus - Potent vasoconstrictor effect and existence in endothelial cells

Takashi Miyauchi, Yoko Tomobe, Reiko Shiba, Tomohisa Ishikawa, Masashi Yanagisawa, Sadao Kimura, Yasuro Sugishita, Iwao Ito, Katsutoshi Goto, Tomoh Masaki

Research output: Contribution to journalArticlepeer-review

126 Scopus citations


Endothelin, a recently discovered endothelium-derived peptide, has been reported to produce potent vasoconstriction in various vessels of experimental animals. To study the involvement of endothelin in the regulation of vascular tonus in humans, isolated human mesenteric arteries were investigated by both pharmacological and immunohistochemical methods. The vasoconstrictor action of endothelin-1 was examined on ring segments of human mesenteric arteries. Endothelin-1 induced a slowly developing and sustained contraction, with an EC50 value (half-maximal effective concentration) of 2.9×10-9 M, two orders of magnitude smaller than that of norepinephrine (EC50 of 3.9 × 10-7 M), indicating that the vasoconstrictor action of endothelin-1 is about 100 times more potent than that of norepinephrine. The contractile effect of endothelin-1 was affected neither by adrenergic, cholinergic, histaminergic, nor serotonergic antagonists, nor by inhibitors of arachidonic acid metabolism. The vasoconstrictor response to endothelin-1 was effectively antagonized by nicardipine, a dihydropyridine Ca2+ channel blocker. Endothelin-1 profoundly augmented contractile response to Ca2+ in partially depolarized tissues. Immunohistochemical studies revealed for the first time that endothelin-like immunoreactivity was localized in endothelial cells of human mesenteric artery. The results of the present study indicate that endothelin-1 is one of the most potent vasoconstrictors in the human mesenteric artery and that it induces vasoconstriction via an ultimately accelerating Ca2+ influx through voltage-dependent Ca2+ channels. Since endothelin-1 can be located in human endothelial cells, it may play an important physiological or pathophysiological role.

Original languageEnglish (US)
Pages (from-to)1874-1880
Number of pages7
Issue number6
StatePublished - 1990

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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