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. 1993 Oct;92(4):2080–2085. doi: 10.1172/JCI116805

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

K Yokokawa 1, H Tahara 1, M Kohno 1, A K Mandal 1, M Yanagisawa 1, T Takeda 1
PMCID: PMC288378  PMID: 8408661

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.

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Selected References

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