title: Neuronal nitric oxide synthase-derived hydrogen peroxide effect in grafts used in human coronary bypass surgery.
abstract: Recently, H2O2has 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 H2O2The role of nNOS-derived H2O2in human vessels is so far unknown. The present study was aimed at investigating the relevance of nNOS/H2O2signaling 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 H2O2Superoxide dismutase (SOD), which generates H2O2from 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 H2O2produced vasodilatation in IMA, it constricted SV. ACh increased H2O2production in both sets of vessels. In the IMA, the increase in H2O2was inhibited by catalase and nNOS blockade. In SV, H2O2production 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 H2O2induced endothelium-dependent vascular relaxation in the IMA, whereas, in the SV, H2O2was a vasoconstrictor. Thus, H2O2produced 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.
authors.affiliation: Department of Physiology and Biophysics, Biological Sciences Institute, Universidade Federal de Minas Gerais, Brazil.
authors.forename: Patrick Wander
authors.initials: PW
authors.lastname: Endlich
authors.affiliation: Department of Physiology and Biophysics, Biological Sciences Institute, Universidade Federal de Minas Gerais, Brazil.
authors.forename: Rosária Dias
authors.initials: RD
authors.lastname: Aires
authors.affiliation: Department of Physiology and Biophysics, Biological Sciences Institute, Universidade Federal de Minas Gerais, Brazil.
authors.forename: Roberta Lins
authors.initials: RL
authors.lastname: Gonçalves
authors.affiliation: Department of Physiology and Biophysics, Biological Sciences Institute, Universidade Federal de Minas Gerais, Brazil.
authors.forename: Eduardo Damasceno
authors.initials: ED
authors.lastname: Costa
authors.affiliation: Faculdade de Ciências Médicas de Minas Gerais. Alameda Ezequiel Dias, 275, Belo Horizonte, MG, Brazil. Zipcode: 30130-110.
authors.forename: Janaína
authors.initials: J
authors.lastname: de Paula Arantes Ângelo
authors.affiliation: Department of Physiology and Biophysics, Biological Sciences Institute, Universidade Federal de Minas Gerais, Brazil.
authors.forename: Lucas Ferreira
authors.initials: LF
authors.lastname: Alves
authors.affiliation: Department of Physiology and Biophysics, Biological Sciences Institute, Universidade Federal de Minas Gerais, Brazil.
authors.forename: Rafaela Fernandes
authors.initials: RF
authors.lastname: da Silva
authors.affiliation: Department of Physiology and Biophysics, Biological Sciences Institute, Universidade Federal de Minas Gerais, Brazil.|Faculdade de Ciências Médicas de Minas Gerais. Alameda Ezequiel Dias, 275, Belo Horizonte, MG, Brazil. Zipcode: 30130-110.
authors.forename: Bruno Almeida
authors.initials: BA
authors.lastname: Rezende
authors.affiliation: Department of Pharmacology, Biological Sciences Institute, Universidade Federal de Minas Gerais. Av. Antônio Carlos, 6627; Pampulha, Belo Horizonte, MG, Brazil. Zipcode: 31270-901.
authors.forename: Steyner F
authors.initials: SF
authors.lastname: Cortes
authors.affiliation: Department of Physiology and Biophysics, Biological Sciences Institute, Universidade Federal de Minas Gerais, Brazil vslemos@icb.ufmg.br.
authors.forename: Virgínia Soares
authors.initials: VS
authors.lastname: Lemos
mesh_terms: D000368:Aged; D001026:Coronary Artery Bypass; D003331:Coronary Vessels / Q000378:metabolism* / Q000601:surgery; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008297:Male; D008323:Mammary Arteries / Q000378:metabolism* / Q000601:surgery; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000235:genetics / Q000378:metabolism*; D012501:Saphenous Vein / Q000378:metabolism* / Q000601:surgery
chemical_list: D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D052248:Nitric Oxide Synthase Type I
keywords: coronary bypass surgery; human mammary artery; human saphenous vein; hydrogen peroxide; nNOS