PREFERENTIAL VASOCONSTRICTION TO CYSTEINYL LEUKOTRIENES IN THE HUMAN SAPHENOUS-VEIN COMPARED WITH THE INTERNAL MAMMARY ARTERY - IMPLICATIONS FOR GRAFT PERFORMANCE

Background Platelet aggregation with the release of their vasoactive m ediators is an important factor contributing to the patency of coronar y bypass grafts. However, the role of leukocyte-derived mediators on g raft performance is unclear. Leukotrienes (LTs) are proinflammatory me diators released from a variety of leukocytes that possess both vasoac tive and mitogenic properties. We have therefore compared the effects of the cysteinyl LTs (C-4, D-4, and E(4)) on the human saphenous vein (SV) and human internal mammary artery (IMA). Methods and Results Huma n SVs from 43 patients (mean age, 58 years) and IMAs from 33 patients (mean age, 57 years) were obtained from individuals undergoing coronar y artery bypass surgery for coronary artery disease. The samples were set up in organ baths to record changes in vessel wall tension in undi stended SVs the cysteinyl LTs elicited concentration-dependent contrac tions. The E(max) for LTE(4) (4.23+/-1.0 mN; n=6) was significantly le ss than that observed with either LTC(4) (25.7+/-4.01 mN; n=7; P<.001) or LTD(4) (26.19+/-3.16 mN; n=7; P<.001). In addition, the LTD(4) rec eptor antagonist ICI 198615 (30 nmol/L) significantly inhibited the LT D(4) concentration-response curve but not the LTC(4) responses. Furthe rmore, treatment of the SV with acivicin (0.05 mmol/L), a gamma-glutam yl transpeptidase inhibitor, caused a significant rightward displaceme nt of the LTC(4) concentration-response curve. In contrast, LTC(4) and LTD(4) produced a response in IMAs from only 3 of 29 patients. LTC(4) and LTD(4) produced small contractions, of which the maximum response s were 3.28+/-1.92 mN (n=5) and 3.12+/-1.38 mN (n=5). LTE(4) produced no responses in the IMA. Experiments in which the SV was pretreated wi th L-N-G-monomethyl-L-arginine (L-NMMA; 10(-4) morn) or indomethacin ( 10(-5) mol/L) or was denuded of endothelium had no significant effect on the E(max) values for LTE(4). Also, the IMA remained unresponsive t o cysteinyl leukotrienes after treatment with L-NMMA or indomethacin o r endothelium removal. In vitro autoradiography localized specific [H- 3]-LTC(4), and [H-3]-LTD(4) binding sites (putative receptors) to the smooth muscle cells of both SV and IMA, with greater binding to the SV . Conclusions Our data show that there is a preferential contraction t o LTs in SV compared with IMA. This difference in smooth muscle cell r eactivity to the cysteinyl LTs suggests that endogenous LT production from circulating or infiltrating leukocytes may be an important factor contributing to graft function.