title: Endothelin-1 shifts the mediator of bradykinin-induced relaxation from NO to H2 O2 in resistance arteries from patients with cardiovascular disease.
abstract: We tested the hypothesis that in resistance arteries from cardiovascular disease (CVD) patients, effects of an endothelium-dependent vasodilator depend on the contractile stimulus.
  
  
  
  Arteries dissected from parietal pericardium of cardiothoracic surgery patients were studied by myography and imaging techniques. Segments were sub-maximally contracted by K(+) , the TxA2 analogue U46619 or endothelin-1 (ET-1).
  
  
  
  Relaxing effects of Na-nitroprusside were comparable, but those of bradykinin (BK) were bigger in the presence of ET-1 compared with K(+) or U46619. BK-induced relaxation was (i) abolished by L-NAME in K(+) -contracted arteries, (ii) partly inhibited by L-NAME in the presence of U46619 and (iii) not altered by indomethacin, L-NAME plus inhibitors of small and intermediate conductance calcium-activated K(+) channels, but attenuated by catalase, in ET-1-contracted arteries. This catalase-sensitive relaxation was unaffected by inhibitors of NADPH oxidases or allopurinol. Exogenous H2 O2 caused a larger relaxation of ET-1-induced contractions than those evoked by K(+) or U46619 in the presence of inhibitors of other endothelium-derived relaxing factors. Catalase-sensitive staining of cellular ROS with CellROX Deep Red was significantly increased in the presence of both 1 μM BK and 2 nM ET-1 but not either peptide alone.
  
  
  
  In resistance arteries from patients with CVD, exogenous ET-1 shifts the mediator of relaxing responses to the endothelium-dependent vasodilator BK from NO to H2 O2 and neither NADPH oxidases, xanthine oxidase nor NOS appear to be involved in this effect. This might have consequences for endothelial dysfunction in conditions where intra-arterial levels of ET-1 are enhanced.
authors.affiliation: Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Leurgans
authors.affiliation: Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
authors.forename: Maria
authors.initials: M
authors.lastname: Bloksgaard
authors.affiliation: Department of Biochemistry and Molecular Biology, MEMPHYS-Center for Biomembrane Physics, University of Southern Denmark, Odense, Denmark.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Brewer
authors.affiliation: Department of Biochemistry and Molecular Biology, MEMPHYS-Center for Biomembrane Physics, University of Southern Denmark, Odense, Denmark.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Bagatolli
authors.affiliation: Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
authors.forename: Maise H
authors.initials: MH
authors.lastname: Fredgart
authors.affiliation: Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Rosenstand
authors.affiliation: Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Hansen
authors.affiliation: Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark.|Center for Individualized Medicine in Arterial Diseases (CIMA), Odense University Hospital, Odense, Denmark.
authors.forename: Lars M
authors.initials: LM
authors.lastname: Rasmussen
authors.affiliation: Center for Individualized Medicine in Arterial Diseases (CIMA), Odense University Hospital, Odense, Denmark.|Department of Cardiac, Thoracic and Vascular Surgery, Odense University Hospital, Odense, Denmark.
authors.forename: Akhmadjon
authors.initials: A
authors.lastname: Irmukhamedov
authors.affiliation: Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.|Center for Individualized Medicine in Arterial Diseases (CIMA), Odense University Hospital, Odense, Denmark.|Department of Cardiac, Thoracic and Vascular Surgery, Odense University Hospital, Odense, Denmark.|Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands.
authors.forename: Jo Gr
authors.initials: JG
authors.lastname: De Mey
mesh_terms: D000368:Aged; D001158:Arteries / Q000187:drug effects* / Q000378:metabolism*; D001920:Bradykinin / Q000494:pharmacology*; D002318:Cardiovascular Diseases / Q000378:metabolism*; D019332:Endothelin-1 / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*
chemical_list: D019332:Endothelin-1; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D001920:Bradykinin