Responses of experimental vein grafts to endothelin-1

Vein grafts have altered vasomotor responses to several physiologically important agonists and are susceptible to vasospasm. Endothelin-1 (ET-1) is an endothelium-derived vasoactive polypeptide and a potent vasoconstrictor in most vascular beds. However, the responses of vein grafts to ET-1 are not known. Twenty New Zealand White rabbits underwent right common carotid interposition bypass using the external jugular vein, and these grafts with their contralateral jugular veins were harvested after 28 days. Isometric tension studies were performed on rings from these vessels. ET-1 (10^-12 to 10^-6 M) produced a biphasic dose-response curve in the vein graft: low concentrations induced relaxation followed by contraction at higher concentrations. In contrast, the contralateral vein segments produced a sigmoid-shaped contract on curve to ET-1. The EC₅₀ values for contraction were 8.17 ± 0.08 and 7.52 ± 0.16 (mean ± SEM; -log₁₀[EC₅₀]; p < .01) for the contralateral vein and vein graft, respectively. The contralateral vein generated more active maximal tension than the vein graft (660 ± 11 vs. 260 ± 40 mg; mean ± SEM; p < .01). Both the contralateral vein and vein graft showed a significant loss of contractile response to ET-1 on the second and subsequent applications, but the sensitivity in each tissue was maintained. In prostaglandin F(2α) precontracted tissue, ET-1 induced significantly more relaxation in the contralateral vein (42% ± 9%; maximal relaxation) than the vein graft (20% ± 9%; p < .05). Incubation with ET-1 (10^-8 M for 30 minutes) enhanced the responses to norepinephrine (10^-9 to 10^-5 M) in the contralateral vein but not in the vein graft, while serotonin responses (10^-9 to 10^-5 M) were augmented in the vein graft. This study demonstrates that the responses to ET-1 in vein grafts are significantly attenuated compared with the contralateral veins. In view of the attenuated responses in the vein grafts, the relaxation at low doses of ET-1 and the reduced responses noted to second and subsequent applications, ET-1 appears unlikely to play a major role in the pathophysiology of vein graft spasm.