Heparin regulates endothelin production through endothelium-derived nitric oxide in human endothelial cells

Koji Yokokawa, Hideki Tahara, Masakazu Kohno, Anil K. Mandal, Masashi Yanagisawa, Tadanao Takeda

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112 Scopus citations


Heparin shows blood pressure lowering effect in hypertensive patients and animal models. The present study examined the effect of heparin on vasoconstrictor endothelin-1 (ET-1) production in cultured human umbilical vein endothelial cells (ECs) to elucidate the mechanism of antihypertensive effect of heparin. Heparin suppressed both basal and thrombin-stimulated ET-1 mRNA expression paralleled with a decrease in ET-1 peptide release in a dose-dependent manner. Heparin concomitantly enhanced nitric oxide (NO) formation measured by NO2/NO3 levels and cGMP production in ECs. These enhancements were more marked when ECs were stimulated by thrombin. However, these heparin's effects were blunted in the presence of endothelium-derived nitric oxide (EDNO) synthesizing inhibitor NG-monomethyl L-arginine. Therefore, these results suggest that suppression of ET-1 production by heparin is EDNO mediated.

Original languageEnglish (US)
Pages (from-to)2080-2085
Number of pages6
JournalJournal of Clinical Investigation
Issue number4
Publication statusPublished - 1993



  • Endothelial cell
  • Endothelin
  • Endothelium-derived nitric oxide
  • Heparin
  • N-monomethyl l-arginine

ASJC Scopus subject areas

  • Medicine(all)

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