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

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Abstract

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.

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