Endothelins: vasoconstrictor effects and localization in canine cerebral arteries

Br J Pharmacol. 1991 May;103(1):1129-35. doi: 10.1111/j.1476-5381.1991.tb12312.x.

Abstract

1. The vascular effects of endothelin and localization of endothelin-like immunoreactivity were characterized in isolated cerebral arteries of dogs. 2. Endothelin-like immunoreactivity was detected in a few populations of endothelial cells of dog basilar artery. 3. 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). 4. 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. 5. 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 Ca(2+)-free solutions although high concentrations of endothelin-1 and endothelin-2 still evoked contractions. 6. 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 vasconstrictor responses to high concentrations of endothelin-1 and endothelin-2. 7. The presence of endothelin-like immunoreactivity in endothelial cells suggests that endothelin is a potential endogenous spasmogen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / physiology
  • Cerebral Arteries / drug effects*
  • Cerebrovascular Circulation / drug effects
  • Dogs
  • Endothelins / pharmacology*
  • Female
  • Immunohistochemistry
  • In Vitro Techniques
  • Male
  • Muscle, Smooth, Vascular / drug effects*
  • Nicardipine / pharmacology
  • Nickel / pharmacology
  • Vasoconstriction / drug effects*

Substances

  • Endothelins
  • nickel chloride
  • Nickel
  • Nicardipine
  • Calcium