Vascular smooth muscle cell effect on endothelial cell endothelin-1 production

J Vasc Surg. 2000 Apr;31(4):781-9. doi: 10.1067/mva.2000.103788.


Endothelin-1 (ET-1) is a potent mitogen secreted by endothelial cells (ECs) in culture and is a putative factor in vascular lesion development. The purpose of this study was to examine whether smooth muscle cells (SMCs) inhibit EC secretion of ET-1. The effect of SMCs on EC ET-1 and constitutively expressed nitric oxide (NO) synthase activity was examined by using a bilayer co-culture model. SMCs inhibited both EC ET-1 protein and RNA levels, compared with ECs cultured alone. SMCs increased EC NO production when compared with ECs cultured alone. In addition, SMC inhibition of EC ET-1 production could be blocked by the NO synthase inhibitor N(G)-nitro-L-arginine-methyl ester. ECs stimulated SMC proliferation, and the ET-1 AB and B receptor blockers inhibited EC stimulation of SMC proliferation. The ET-1 A blocker had no effect on SMC proliferation. We conclude that SMCs regulate EC ET-1 and ecNOS synthase transcript levels and protein levels. SMC inhibition of ET-1 production by ECs may be mediated through SMC-modulated changes in EC NO activity. Finally, EC stimulation of SMC proliferation in bilayer co-culture is mediated by ET-1 through the ET-1 B receptor.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Analysis of Variance
  • Animals
  • Aorta
  • Cattle
  • Cell Division / drug effects
  • Cells, Cultured
  • Coculture Techniques
  • Endothelin Receptor Antagonists
  • Endothelin-1 / antagonists & inhibitors
  • Endothelin-1 / biosynthesis*
  • Endothelin-1 / genetics
  • Endothelin-1 / metabolism
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / enzymology
  • Endothelium, Vascular / metabolism*
  • Enzyme Inhibitors / pharmacology
  • Muscle, Smooth, Vascular / cytology*
  • Muscle, Smooth, Vascular / drug effects
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / biosynthesis
  • Oligopeptides / pharmacology
  • RNA / analysis
  • RNA / genetics
  • Transcription, Genetic


  • Endothelin Receptor Antagonists
  • Endothelin-1
  • Enzyme Inhibitors
  • Oligopeptides
  • BQ 610
  • PD 145065
  • RNA
  • Nitric Oxide Synthase
  • NG-Nitroarginine Methyl Ester