Effect of heparin on endothelin-1 production by cultured human endothelial cells.
Heparin shows a blood pressure-lowering effect in various hypertensive rat models. This study was designed to examine the effect of heparin on vasoconstrictor endothelin-1 (ET-1) production by cultured human umbilical vein endothelial cells (HUVECs). ET-1 and cyclic GMP levels in the medium were determined by radioimmunoassay. ET-1 mRNA was quantified by densitometric Northern blot analysis. ET-1 was released into the medium in a time-dependent manner, and its release was augmented by thrombin (10 U/ml). Heparin suppressed both basal and thrombin-stimulated ET-1 secretion and its mRNA expression in a dose-dependent manner. Heparin suppressed ET-1 mRNA expression in a time-dependent fashion. Heparin did not suppress both basal and thrombin-stimulated ET-1 production in the presence of NG-monomethyl-L-arginine (L-NMMA) (10(-5) M). The production of cGMP stimulated by thrombin was significantly enhanced by heparin, but not in the presence of L-NMMA (10(-5) M). Heparin may suppress vasoconstrictor ET-1 production mediated by the enhancement of endothelium-derived nitric oxide in HUVECs.
Yokokawa
K
K
First Department of Internal Medicine, Osaka City University Medical School, Japan.
Kohno
M
M
Tahara
H
H
Mandal
A K
AK
Yasunari
K
K
Murakawa
K
K
Horio
T
T
Ikeda
M
M
Minami
M
M
Takeda
T
T
D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D006152:Cyclic GMP / Q000096:biosynthesis; D003720:Densitometry; D016232:Endothelins / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D009569:Nitric Oxide / Q000502:physiology; D011247:Pregnancy; D012333:RNA, Messenger / Q000302:isolation & purification; D014471:Umbilical Veins / Q000187:drug effects / Q000378:metabolism
D016232:Endothelins; D012333:RNA, Messenger; D009569:Nitric Oxide; D006493:Heparin; D006152:Cyclic GMP