Reactivity of endothelin-1 on human and canine large veins compared with large arteries in vitro

In comparison with snake venom sarafotoxins S6, the novel, 21-amino acid peptide, endothelin may have selective coronary artery vasoconstrictor actions. We examined endothelin-1 (ET-1) in vitro in five pairs of large arteries and veins from the greyhound dog; (coronary, internal mammary, mesenteric, renal and femoral) as well as the human forearm vein and internal mammary artery and vein. ET-1 caused concentration-dependent, tonic contractions in each pair of vessels, with EC50s significantly lower (5-10 times more sensitive) in each vein compared with the corresponding artery. The coronary artery did not show selective sensitivity to ET-1. For all veins the maximal contraction to ET-1 was approximately 100% that of the maximal contraction (Fmax) achieved with K+ depolarization. In the arteries, however, the Fmax for ET-1 ranged from only 25 to 80% of K+. The contraction responses to ET-1 in all arteries and veins were well maintained after repeated washing with ET-1-free medium. In the dog coronary artery the contraction curve to ET-1 (0.1-30 nM) was endothelium-independent. At the higher concentrations (10-100 nM), however, the peptide often induced transient, endothelium-dependent relaxations prior to the development of the tonic contractions. These results demonstrate that ET-1 is a more potent and efficacious constrictor of large veins than arteries and at high concentrations can release endothelium-derived relaxing factor-like activity from large arteries.