S‐Nitrosothiols cause prolonged, nitric oxide‐mediated relaxation in human saphenous vein and internal mammary artery: therapeutic potential in bypass surgery

Abstract

1 Reduced endothelial nitric oxide (NO) production in conduit vessels for coronary artery bypass grafting (CABG) has been implicated in post-operative complications, including spasm. 2 The brief eects of existing NO donors limits their applicability to improving patency of graft vessels. RIG200 is a novel S-nitrosothiol that might have advantages over conventional drugs because it has sustained eects in areas of endothelial damage. 3 Here we tested the hypothesis that RIG200 and S-nitrosoglutathione (GSNO) have prolonged, NO-mediated eects in human saphenous vein (SV) and internal mammary artery (IMA), compared with glyceryl trinitrate (GTN) and sodium nitroprusside (SNP). 4 84 SV and 80 IMA rings from 64 patients undergoing CABG were studied in vitro. Rings were precontracted with phenylephrine (EC 80 concentration) and the functional integrity of the endothelium tested with acetylcholine (10 mM). 5 Relaxation of precontracted SV and IMA rings to GTN and SNP (0.01 ± 10 mM) generally recovered fully on washout. In contrast, responses to RIG200 and GSNO were sustained during washout (30 min). Sustained relaxation was reversed by the NO scavenger, ferrohaemoglobin (10 mM) but not by the NO synthase inhibitor, N o -nitro-L-arginine methyl ester (100 and 250 mM in SV and IMA respectively). 6 Pretreatment (30 min) of SV with both S-nitrosothiols (10 mM) inhibited phenylephrine-induced contraction for 4180 min, compared with 590 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.

Inhibition of human platelet aggregation by a novel S‐nitrosothiol is abolished by haemoglobin and red blood cells in vitro: implications for anti‐thrombotic therapy

“…RIG200 is considerably more stable than the parent compound, Snitroso-N-acetylpenicillamine (SNAP; Megson et al, 1997) and S-nitrosocysteine, and causes prolonged vasodilatation in endothelium-denuded rat femoral arteries (Megson et al, 1997) and in human bypass graft veins (Sogo et al, 2000). Experiments were performed to determine whether the antiplatelet eects seen with RIG200 and GSNO in PRP are reproduced in whole blood and to establish the in¯uence of RBCs, and the Hb they contain, on the fate of NO generated from S-nitrosothiols.…”

Oxidative and Nitrosative Stress in the Ischemic Acute Renal Failure

“…The abundance of S-nitrosothiols in plasma compared with that of nitric oxide (3-to 4-fold) (Stamler et al, 1992a) suggests that plasma S-nitrosothiols may serve as a reservoir of nitric oxide, acting as an effective buffer (Lhuillier et al, 2003). This has also been shown in vascular tissue (Muller et al, 1996), where S-nitrosothiols are known to cause a prolonged nitric oxide-dependent relaxation (Sogo et al, 2000). These facts led us to hypothesize that renal ischemia induces an increase in tissue nitric oxide levels likely coming from tissue nitrosothiol stores and therefore that this phenomenon should be dependent on the presence of thiol groups in the tissue.…”

“…This is not surprising because nitric oxide synthase requires molecular oxygen. Therefore, during ischemia, nitric oxide must be released from other sources, such as tissue nitric oxide stores (Muller et al, 1996;Rodriguez et al, 2003;Sogo et al, 2000).…”

Nova técnica cirúrgica de preparo da veia safena para revascularização do miocárdio sem manipulação direta - no-touch

“…Many advances have come from medical therapy, pharmacological agents 12 , and genetic therapy 13 , and have undergone constant improvement. Surgical techniques to obtain the SV without important damage to the venous wall during the operation may represent an important improvement.…”