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 mediators is an important factor contributing to the patency of coronary bypass grafts. However, the role of leukocyte-derived mediators on graft performance is unclear. Leukotrienes (LTs) are proinflammatory mediators released from a variety of leukocytes that possess both vasoactive 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 Human SVs from 43 patients (mean age, 58 years) and IMAs from 33 patients (mean age, 57 years) were obtained from individuals undergoing coronary artery bypass surgery for coronary artery disease. The samples were set up in organ baths to record changes in vessel wall tension in undistended SVs the cysteinyl LTs elicited concentration-dependent contractions. The E(max) for LTE(4) (4.23+/-1.0 mN; n=6) was significantly less 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) receptor antagonist ICI 198615 (30 nmol/L) significantly inhibited the LTD(4) concentration-response curve but not the LTC(4) responses. Furthermore, treatment of the SV with acivicin (0.05 mmol/L), a gamma-glutamyl transpeptidase inhibitor, caused a significant rightward displacement 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 responses 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 with 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 to cysteinyl leukotrienes after treatment with L-NMMA or indomethacin or 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 to LTs in SV compared with IMA. This difference in smooth muscle cell reactivity to the cysteinyl LTs suggests that endogenous LT production from circulating or infiltrating leukocytes may be an important factor contributing to graft function.