Endothelin is a potent long-lasting vasoconstrictor in men

Endothelin, a 21-amino acid peptide synthesized by cultured porcine aortic endothelial cells, has recently been identified and shown to produce a potent and prolonged constriction of mammalian blood vessels in vitro. We have studied the effect of local infusion of this peptide on resistance and capacitance vessels of normal volunteers. Infusion of endothelin (5 pmol/min) reduced forearm blood flow by 39 +/- 7% from control observations. The maximum response was seen after approximately 55 min of infusion. After stopping the infusion, return of flow to basal values took approximately 120 min. This contrasts with the short onset and duration of action observed when angiotensin II was infused. During coinfusion studies, reversal by nicardipine (0.3-10 micrograms/min) occurred at similar concentrations in both endothelin-induced and angiotensin-induced flow reduction. This observation suggests that nicardipine nonspecifically antagonizes the flow-reducing effects of endothelin. A pattern of slow onset of constriction was found on local infusion of endothelin (5 pmol/min) into dorsal hand veins. During coinfusion of nicardipine (1.5 microgram/min), no reversal of endothelin-induced (5 pmol/min) constriction of dorsal hand veins occurred. The pharmacological profile of this peptide in the peripheral circulation of humans suggests that it may be involved in long-term regulation of vascular tone.