Endothelins: vasoconstrictor effects and localization in canine cerebral arteries

A. Saito, R. Shiba, Masashi Yanagisawa, T. Masaki, S. Kimura, K. Yamada, T. Mima, T. Shigeno, K. Goto

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


The vascular effects of endothelin and localization of endothelin‐like immunoreactivity were characterized in isolated cerebral arteries of dogs. Endothelin‐like immunoreactivity was detected in a few populations of endothelial cells of dog basilar artery. Endothelin‐1, endothelin‐2 and endothelin‐3 contracted isolated ring preparations of cerebral arteries in a dose‐dependent manner independently of the presence of endothelium. The ED50 values (and 95% confidence intervals) for the contraction were 411 pm (242–697 pm) and 478 pm (295–776 pm) for endothelin‐1 and endothelin‐2, respectively. Endothelin‐3 induced vascular contraction at a higher concentration (ED50 = 26.5 nm, 95% confidence interval = 15.7–45.7 nm). The increases in tone induced by endothelin‐1 and endothelin‐2 did not return to the resting level after repeated washings, while a rinse with Krebs solution reversed the vasoconstrictor response to endothelin‐3. The endothelins did not cause any vasodilator response in arteries precontracted with uridine 5′‐triphosphate even in the presence of intact endothelial cells. NiCl2 (1 mm) attenuated the contractions induced by endothelin‐3 (10–300 nm) and those to relatively low doses (1 nm) but not higher doses (10–100 nm) of endothelin‐1 and endothelin‐2. The contractions in response to endothelin‐1, endothelin‐2 and endothelin‐3 were greatly attenuated in Ca2+‐free solutions although high concentrations of endothelin‐1 and endothelin‐2 still evoked contractions. These results suggest that the vasoconstriction induced by endothelin‐3 and lower doses of endothelin‐1 and endothelin‐2, largely depends on the influx of Ca2+ ions. The apparent insensitivity to Ni2+ shows that additional distinct mechanisms also operate in the vasoconstrictor responses to high concentrations of endothelin‐1 and endothelin‐2. The presence of endothelin‐like immunoreactivity in endothelial cells suggests that endothelin is a potential endogenous spasmogen. 1991 British Pharmacological Society

Original languageEnglish (US)
Pages (from-to)1129-1135
Number of pages7
JournalBritish Journal of Pharmacology
Issue number1
StatePublished - May 1991


  • Dog cerebral artery
  • endothelin
  • immunohistochemistry
  • nicardipine
  • nickel
  • vasoconstriction

ASJC Scopus subject areas

  • Pharmacology


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