Effect of heparin on endothelin-1 production by cultured human endothelial cells

J Cardiovasc Pharmacol. 1993:22 Suppl 8:S46-8. doi: 10.1097/00005344-199322008-00014.

Abstract

Heparin shows a blood pressure-lowering effect in various hypertensive rat models. This study was designed to examine the effect of heparin on vasoconstrictor endothelin-1 (ET-1) production by cultured human umbilical vein endothelial cells (HUVECs). ET-1 and cyclic GMP levels in the medium were determined by radioimmunoassay. ET-1 mRNA was quantified by densitometric Northern blot analysis. ET-1 was released into the medium in a time-dependent manner, and its release was augmented by thrombin (10 U/ml). Heparin suppressed both basal and thrombin-stimulated ET-1 secretion and its mRNA expression in a dose-dependent manner. Heparin suppressed ET-1 mRNA expression in a time-dependent fashion. Heparin did not suppress both basal and thrombin-stimulated ET-1 production in the presence of NG-monomethyl-L-arginine (L-NMMA) (10(-5) M). The production of cGMP stimulated by thrombin was significantly enhanced by heparin, but not in the presence of L-NMMA (10(-5) M). Heparin may suppress vasoconstrictor ET-1 production mediated by the enhancement of endothelium-derived nitric oxide in HUVECs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Northern
  • Cell Division / drug effects
  • Cyclic GMP / biosynthesis
  • Densitometry
  • Endothelins / biosynthesis*
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism*
  • Female
  • Heparin / pharmacology*
  • Humans
  • Nitric Oxide / physiology
  • Pregnancy
  • RNA, Messenger / isolation & purification
  • Umbilical Veins / drug effects
  • Umbilical Veins / metabolism

Substances

  • Endothelins
  • RNA, Messenger
  • Nitric Oxide
  • Heparin
  • Cyclic GMP