Endothelin-3: selectivity as an anti-aggregatory peptide in vivo

Endothelin-3 (1 nmol/kg) given i.v. to anaesthetised rabbits significantly inhibited ADP-induced ex vivo platelet aggregation, while causing only a transient decrease in blood pressure and no change in heart rate. Pretreatment with piroxicam (14 mumol/kg) abolished the anti-aggregatory effect. Thus, endothelin-3, while not inhibiting rabbit platelets in vitro, can induce the release of a cyclo-oxygenase produce, probably prostacyclin, which inhibits ex vivo aggregation. Unlike endothelin-1, this was achieved with minimal effect on the haemodynamics.