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

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

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
Volume92
Issue number4
StatePublished - 1993

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Endothelins
Heparin
Nitric Oxide
Endothelial Cells
Endothelin-1
Thrombin
omega-N-Methylarginine
Human Umbilical Vein Endothelial Cells
Vasoconstrictor Agents
Antihypertensive Agents
Animal Models
Blood Pressure
Messenger RNA
Peptides

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Heparin regulates endothelin production through endothelium-derived nitric oxide in human endothelial cells. / Yokokawa, Koji; Tahara, Hideki; Kohno, Masakazu; Mandal, Anil K.; Yanagisawa, Masashi; Takeda, Tadanao.

In: Journal of Clinical Investigation, Vol. 92, No. 4, 1993, p. 2080-2085.

Research output: Contribution to journalArticle

Yokokawa, Koji ; Tahara, Hideki ; Kohno, Masakazu ; Mandal, Anil K. ; Yanagisawa, Masashi ; Takeda, Tadanao. / Heparin regulates endothelin production through endothelium-derived nitric oxide in human endothelial cells. In: Journal of Clinical Investigation. 1993 ; Vol. 92, No. 4. pp. 2080-2085.
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N2 - 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.

AB - 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.

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