Effects of leukotrienes C₄ and D₄ on human isolates saphenous veins

Allen, Sean P., Chester, Adrian H., Piper, Priscilla J., Sampson, Anthony P., Akl, El Sayed K. and Yacoub, Madgi H. (1992) Effects of leukotrienes C₄ and D₄ on human isolates saphenous veins. British Journal of Clinical Pharmacology, 34 (5), 409-414.

Abstract

Vascular injury during the intra-operative procedures of bypass surgery may be the initiating event in the gradual deterioration in the patency of the graft. Adhesion of leukocytes to the vascular endothelium frequently accompanies preparation and insertion of the graft. However, little is known about the effects of vasoactive substances released from leukocytes on vein graft performance. To determine whether leukotrienes are capable of affecting the tone of blood vessels used as coronary artery bypass grafts we studied the human saphenous vein as intact rings using an isolated organ bath technique. LTC₄ and LTD₄ caused weak endothelium-dependent relaxations at lower concentrations (1 pM to 1 nM) and powerful endothelium-independent contractions at higher concentrations (3 nM to 0.1 μM). The maximum responses to LTC₄ and LTD₄ for relaxations were 21.1 ± 4.8% and 28.6 ± 3.4% (% of noradrenaline induced tone) respectively and 64.6 ± 9.9% and 59.1 ± 7.9% (% response to KCl) respectively for contractions. The inhibitor of nitric oxide formation, L-N(G)-monomethyl L-arginine, prevented the relaxations to LTD₄, but not LTC₄ and unmasked endothelium-dependent contractions to LTD₄ (32.9 ± 11.3%). N(G)-monomethyl L-arginine had no effect on the contractions produced by LTC₄ or LTD₄. Indomethacin augmented relaxations and contractions of saphenous vein to LTC₄ from 22.5 ± 5.6 to 40.02 ± 8.7 (P < 0.05) and 48.8 ± 5.5% to 74.7 ± 7.6% (P < 0.01) respectively. LTD₄ responses were not affected by indomethacin treatment. In conclusion, leukotrienes mediate biphasic responses in the human saphenous vein. The pronounced constriction of saphenous veins with LTC₄ and LTD₄ suggest that leukotrienes derived from leukocytes and/or the vessel wall may modulate flow in the saphenous vein and possibly influence early and/or long term vein graft patency.

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Contributors

Author: Anthony P. Sampson

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