Contractile effect of endothelin-2 on the isolated human saphenous vein

The contractile effect of endothelin-2 was investigated in isolated human saphenous vein preparations. Spare segments taken from revascularized patients were set up in isolated organ chambers and mechanical activity was recorded under isometric conditions. Endothelin-2 (10(-11)-10(-7) M) evoked a dose-dependent contractile response, having the same efficacy as noradrenaline and 100 times its potency. Conversely, the "selective" ETB agonist, C-terminal hexapeptide endothelin (16-21), was completely ineffective. The activity of endothelin-2 was not modified by phentolamine, saralasin and indomethacin, thus excluding a direct or indirect activation of alpha-adrenoceptors and angiotensin receptors as well as the synthesis of cyclooxygenase products. Calcium removal from nutrient fluid depressed, but not fully abolished, the contractile effect of endothelin-2; furthermore, calcium channel blockers, verapamil and nifedipine, produced only a partial inhibition of the endothelin-2-induced contractions. These observations suggest that endothelin-2 induces a direct activation of specific receptors in the saphenous vein muscle and that both intracellular and extracellular calcium pools may be involved in the contractile effect of the peptide.