Contribution of endogenous generation of endothelin-1 to basal vascular tone

William G Haynes, David J Webb

Research output: Contribution to journalArticlepeer-review

Abstract

Summary
Endothelin-1 is an endothelium-derived vasoconstrictor peptide, possibly involved in the pathophysiology of cardiovascular disease. We examined the contribution of endogenously generated endothelin-1 to maintenance of peripheral vascular tone in healthy subjects by local intra-arterial administration of an inhibitor of endothelin converting enzyme, phosphoramidon, and of a selective endothelin receptor A antagonist, BQ-123.
Brachial artery infusion of local doses of proendothelin-1, the precursor to endothelin-1, caused a slow-onset dose-dependent forearm vasoconstriction which was abolished by co-infusion of phosphoramidon. Phosphoramidon did not affect responses to endothelin-1. Phosphoramidon caused slow-onset vasodilatation when infused alone, with blood flow increasing by 37% at 90 min (p=0·03). Vasoconstriction to endothelin-1 was abolished by co-infusion of BQ-123 (p=0·006), with forearm blood flow tending to increase. Infusion of BQ-123 alone caused progressive vasodilatation, with blood flow increasing by 64% after 60 min (p=0·007).
These results show that endogenous production of endothelin-1 contributes to the maintenance of vascular tone. Endothelin converting enzyme inhibitors and receptor antagonists may have therapeutic potential as vasodilators.
Original languageEnglish
Pages (from-to)852-854
JournalThe Lancet
Volume344
Issue number8926
DOIs
Publication statusPublished - 24 Sep 1994

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