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

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.