ENDOTHELIUM-DEPENDENT MODULATION OF RESPONSES TO ENDOTHELIN-I IN HUMAN VEINS

被引:53
作者
HAYNES, WG
WEBB, DJ
机构
[1] University of Edinburgh, Department of Medicine, Western General Hospital, Edinburgh EH4 2XU, Crewe Road
关键词
ASPIRIN; ENDOTHELIUM; NG-MONOMETHYL-L-ARGININE; NITRIC OXIDE; PROSTACYCLIN; PROSTAGLANDINS; VEINS;
D O I
10.1042/cs0840427
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
1. We have investigated whether local vascular production of nitric oxide or prostacyclin regulates venoconstriction induced by the endothelium-derived peptide, endothelin-1, in vivo in man. 2. Six healthy subjects received local dorsal hand vein infusion of endothelin-1 for 60 min alone or, on two separate occasions, co-infused with the donator of nitric oxide, glyceryl trinitrate, or the vasodilator prostaglandin, prostacyclin. In further studies, endothelin-I was co-infused with an inhibitor of nitric oxide production, N(G)-monomethyl-L-arginine, or after oral administration of the irreversible inhibitor of prostaglandin production, acetylsalicylic acid (aspirin). 3. At a low dose (5 pmol/min), endothelin-1 alone caused slowly developing and long-lasting venoconstriction (maximal constriction: 66 +/- 4%). Although glyceryl trinitrate partially prevented endothelin-1-induced venoconstriction (maximum: 33 +/- 5%), inhibition of nitric oxide production did not affect endothelin-1-induced venoconstriction (maximum: 55 +/- 4%). 4. Prostacyclin was more effective at blocking the venoconstriction in response to endothelin-I than glyceryl trinitrate (maximum: 12 +/- 3%), and there was substantial potentiation of endothelin-1-induced venoconstriction after pretreatment with aspirin (maximum: 90 +/- 3%). 5. Despite the capacity of nitric oxide to attenuate responses to endothelin-1, N(G)-monomethyl-L-arginine did not potentiate endothelin-1-induced venoconstriction, suggesting little or no stimulated production of nitric oxide in human veins. However, the potentiation of responses to endothelin-I by aspirin indicates that endothelial production of prostacyclin attenuates responses to endothelin-1 in human veins in vivo.
引用
收藏
页码:427 / 433
页数:7
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