Mechanism of contraction to endothelin in isolated porcine coronary artery

Y. Kasuya, T. Ishikawa, Masashi Yanagisawa, S. Kimura, K. Goto, T. Masaki

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

To elucidate the mechanisms of action of endothelin (ET) on vascular smooth muscles, the contractile responses of the isolated porcine coronary artery to ET were precisely investigated. ET produced concentration-dependent vasoconstrictions that were not mediated by biogenic amines, arachidonate metabolites, or endothelium-derived contractile factors. The maximum response to ET was identical to the response to K+ depolarization. The vasoconstrictor activity of ET was at least one or two orders of magnitude more potent than other vasoconstrictors (BAY K 8644, histamine, acetylcholine, and prostaglandin F(2α)) examined. The action of ET was antagonized by a dihydropyridine Ca2+ antagonist, nicardipine, in a competitive fashion. ET-induced vasoconstriction was not mediated by membrane depolarization. A small amount of ET (2 x 10-10 M) caused a leftward shift of the concentration-response relationship for K+. ET (5 x 10-10, 5 x 10-8 M) accelerated 45Ca2+ uptake to the smooth muscle cells, which were inhibited by nicardipine. However, ET did not affect the specific binding of [125I]iodipine to the smooth muscle cell membrane. These results suggest that ET produces vasoconstriction via ultimately accelerating Ca2+ influx through voltage-dependent Ca2+ channels but that the binding site is distinct from that of dihydropyridines.

Original languageEnglish (US)
Pages (from-to)26/6
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume257
Issue number6
StatePublished - Dec 1 1989

Keywords

  • calcium antagonists
  • calcium uptake
  • endothelin receptor binding
  • membrane potential

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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