Affiliation:
1. University of Edinburgh, Department of Medicine, Western General Hospital, Edinburgh, U.K.
Abstract
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-l was co-infused with an inhibitor of nitric oxide production, NG-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-1 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, NG-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-1 by aspirin indicates that endothelial production of prostacyclin attenuates responses to endothelin-1 in human veins in vivo.
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58 articles.
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