TY - JOUR
T1 - Involvement of endothelin in the regulation of human vascular tonus - Potent vasoconstrictor effect and existence in endothelial cells
AU - Miyauchi, Takashi
AU - Tomobe, Yoko
AU - Shiba, Reiko
AU - Ishikawa, Tomohisa
AU - Yanagisawa, Masashi
AU - Kimura, Sadao
AU - Sugishita, Yasuro
AU - Ito, Iwao
AU - Goto, Katsutoshi
AU - Masaki, Tomoh
PY - 1990
Y1 - 1990
N2 - 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.
AB - 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.
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U2 - 10.1161/01.CIR.81.6.1874
DO - 10.1161/01.CIR.81.6.1874
M3 - Article
C2 - 2188755
AN - SCOPUS:0025358314
SN - 0009-7322
VL - 81
SP - 1874
EP - 1880
JO - Circulation
JF - Circulation
IS - 6
ER -