HEPARIN REGULATES ENDOTHELIN PRODUCTION THROUGH ENDOTHELIUM-DERIVED NITRIC-OXIDE IN HUMAN ENDOTHELIAL-CELLS

被引:105
作者
YOKOKAWA, K
TAHARA, H
KOHNO, M
MANDAL, AK
YANAGISAWA, M
TAKEDA, T
机构
[1] UNIV TEXAS, SW MED CTR, DEPT MOLEC GENE, DALLAS, TX 75235 USA
[2] UNIV TEXAS, SW MED CTR, HOWARD HUGHES MED INST, DALLAS, TX 75235 USA
[3] OSAKA CITY UNIV, SCH MED, DEPT INTERNAL MED 2, ABENO KU, OSAKA 545, JAPAN
[4] WRIGHT STATE UNIV, DEPT MED, DAYTON, OH 45435 USA
[5] VET AFFAIRS MED CTR, DAYTON, OH 45428 USA
关键词
ENDOTHELIN; HEPARIN; ENDOTHELIAL CELL; ENDOTHELIUM-DERIVED NITRIC OXIDE; NG-MONOMETHYL L-ARGININE;
D O I
10.1172/JCI116805
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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 N(G)-monomethyl L-arginine. Therefore, these results suggest that suppression of ET-1 production by heparin is EDNO mediated.
引用
收藏
页码:2080 / 2085
页数:6
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