Heparin regulates endothelin production through endothelium-derived nitric oxide in human endothelial cells.
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.
Yokokawa
K
K
First Department of Internal Medicine, Osaka City University Medical School, Japan.
Tahara
H
H
Kohno
M
M
Mandal
A K
AK
Yanagisawa
M
M
Takeda
T
T
D000704:Analysis of Variance; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D015152:Blotting, Northern; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D003609:Dactinomycin / Q000494:pharmacology; D016232:Endothelins / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D009569:Nitric Oxide / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology; D013997:Time Factors; D014471:Umbilical Veins; D019323:omega-N-Methylarginine
D016232:Endothelins; D012333:RNA, Messenger; D003609:Dactinomycin; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D006493:Heparin; D001120:Arginine; D013917:Thrombin; D006152:Cyclic GMP