Recently, H2O2 has been identified as the endothelium-dependent hyperpolarizing factor (EDHF), which mediates flow-induced dilation in human coronary arteries. Neuronal nitric oxide synthase (nNOS) is expressed in the cardiovascular system and, besides NO, generates H2O2. The role of nNOS-derived H2O2 in human vessels is so far unknown. The present study was aimed at investigating the relevance of nNOS/H2O2 signaling in the human internal mammary artery (IMA) and saphenous vein (SV), the major conduits used in coronary artery bypass grafting. In the IMA, but not in the SV, ACh (acetylcholine)-induced vasodilatation was decreased by selective nNOS inhibition with TRIM or Inhibitor 1, and by catalase, which specifically decomposes H2O2. Superoxide dismutase (SOD), which generates H2O2 from superoxide, decreased the vasodilator effect of ACh on SV. In the IMA, SOD diminished phenylephrine-induced contraction in endothelium-containing, but not in endothelium-denuded vessels. Importantly, while exogenous H2O2 produced vasodilatation in IMA, it constricted SV. ACh increased H2O2 production in both sets of vessels. In the IMA, the increase in H2O2 was inhibited by catalase and nNOS blockade. In SV, H2O2 production was abolished by catalase and reduced by nNOS inhibition. Immunofluorescence experiments showed the presence of nNOS in the vascular endothelium and smooth muscle cells of both the IMA and SV. Together, our results clearly show that H2O2 induced endothelium-dependent vascular relaxation in the IMA, whereas, in the SV, H2O2 was a vasoconstrictor. Thus, H2O2 produced in the coronary circulation may contribute to the susceptibility to accelerated atherosclerosis and progressive failure of the SV used as autogenous graft in coronary bypass surgery.
Neuronal nitric oxide synthase-derived hydrogen peroxide effect in grafts used in human coronary bypass surgery
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Patrick Wander Endlich, Rosária Dias Aires, Roberta Lins Gonçalves, Eduardo Damasceno Costa, Janaína de Paula Arantes Ângelo, Lucas Ferreira Alves, Rafaela Fernandes da Silva, Bruno Almeida Rezende, Steyner F. Cortes, Virgínia Soares Lemos; Neuronal nitric oxide synthase-derived hydrogen peroxide effect in grafts used in human coronary bypass surgery. Clin Sci (Lond) 1 May 2017; 131 (10): 1015–1026. doi: https://doi.org/10.1042/CS20160642
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