S-nitrosothiols cause prolonged, nitric oxide-mediated relaxation in humansaphenous vein and internal mammary artery: therapeutic potential in bypass surgery

1 Reduced endothelial nitric oxide (NO) production in conduit vessels for c oronary artery bypass grafting (CABG) has been implicated in post-operative complications, including spasm. 2 The brief effects of existing NO donors limits their applicability to imp roving patency of graft vessels. RIG200 is a novel S-nitrosothiol that migh t have advantages over conventional drugs because it has sustained effects in areas of endothelial damage. 3 Here we tested the hypothesis that RIG200 and S-nitrosoglutathione (GSNO) have prolonged, NO-mediated effects in human saphenous vein (SV) and inter nal mammary artery (IMA), compared with glyceryl trinitrate (GTN) and sodiu m nitroprusside (SNP). 4 84 SV and 80 IMA rings from 64 patients undergoing CABG were studied in v itro. Rings were precontracted with phenylephrine (EC80 concentration) and the functional integrity of the endothelium tested with acetylcholine (10 m uM). 5 Relaxation of precontracted SV and IMA rings to GTN and SNP (0.01 - 10 mu M) generally recovered fully on washout. In contrast, responses to RIG200 a nd GSNO were sustained during washout (30 min). Sustained relaxation was re versed by the NO scavenger, ferrohaemoglobin (10 muM) but not by the NO syn thase inhibitor, N-omega-nitro-L-arginine methyl ester (100 and 250 muM in SV and IMA respectively). 6 Pretreatment (30 min) of SV with both S-nitrosothiols (10 muM) inhibited phenylephrine-induced contraction for > 180 min, compared with < 90 min for GTN. In IMA, contractility was suppressed to 49 +/- 4% (GSNO) and 26 +/- 4 % (RIG200) of baseline after 240 min washout. 7 Pretreatment of bypass conduits with S-nitrosothiols might improve their patency in the early post-operative period.