title: Nitric Oxide Resistance Reduces Arteriovenous Fistula Maturation in Chronic Kidney Disease in Rats.
abstract: BACKGROUND
  Autologous arteriovenous (AV) fistulas are the first choice for vascular access but have a high risk of non-maturation due to insufficient vessel adaptation, a process dependent on nitric oxide (NO)-signaling. Chronic kidney disease (CKD) is associated with oxidative stress that can disturb NO-signaling. Here, we evaluated the influence of CKD on AV fistula maturation and NO-signaling.
  
  
  METHODS
  CKD was established in rats by a 5/6th nephrectomy and after 6 weeks, an AV fistula was created between the carotid artery and jugular vein, which was followed up at 3 weeks with ultrasound and flow assessments. Vessel wall histology was assessed afterwards and vasoreactivity of carotid arteries was studied in a wire myograph. The soluble guanylate cyclase (sGC) activator BAY 60-2770 was administered daily to CKD animals for 3 weeks to enhance fistula maturation.
  
  
  RESULTS
  CKD animals showed lower flow rates, smaller fistula diameters and increased oxidative stress levels in the vessel wall. Endothelium-dependent relaxation was comparable but vasorelaxation after sodium nitroprusside was diminished in CKD vessels, indicating NO resistance of the NO-receptor sGC. This was confirmed by stimulation with BAY 60-2770 resulting in increased vasorelaxation in CKD vessels. Oral administration of BAY 60-2770 to CKD animals induced larger fistula diameters, however; flow was not significantly different from vehicle-treated CKD animals.
  
  
  CONCLUSIONS
  CKD induces oxidative stress resulting in NO resistance that can hamper AV fistula maturation. sGC activators like BAY 60-2770 could offer therapeutic potential to increase AV fistula maturation.
authors.affiliation: Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands.|Department of General Surgery, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Irma L
authors.initials: IL
authors.lastname: Geenen
authors.affiliation: Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Felix F
authors.initials: FF
authors.lastname: Kolk
authors.affiliation: Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Molin
authors.affiliation: Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Allard
authors.initials: A
authors.lastname: Wagenaar
authors.affiliation: Department of Pharmacology, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Mathijs G
authors.initials: MG
authors.lastname: Compeer
authors.affiliation: Department of General Surgery, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Jan H
authors.initials: JH
authors.lastname: Tordoir
authors.affiliation: Department of General Surgery, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Geert W
authors.initials: GW
authors.lastname: Schurink
authors.affiliation: Department of Pharmacology, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Jo G
authors.initials: JG
authors.lastname: De Mey
authors.affiliation: Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Post
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001166:Arteriovenous Shunt, Surgical; D001565:Benzoates / Q000627:therapeutic use; D001713:Biphenyl Compounds / Q000627:therapeutic use; D002339:Carotid Arteries / Q000187:drug effects / Q000601:surgery; D004351:Drug Resistance; D006162:Guanylate Cyclase / Q000187:drug effects / Q000502:physiology; D006845:Hydrocarbons, Fluorinated / Q000627:therapeutic use; D007601:Jugular Veins / Q000187:drug effects / Q000601:surgery; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009392:Nephrectomy / Q000009:adverse effects; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology* / Q000627:therapeutic use; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology* / Q000627:therapeutic use; D018384:Oxidative Stress; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D051436:Renal Insufficiency, Chronic / Q000503:physiopathology / Q000628:therapy*; D015398:Signal Transduction; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: C528797:4-(((4-carboxybutyl) (2- (5-fluoro-2-((4'-(trifluoromethyl) biphenyl-4-yl)methoxy)phenyl)ethyl) amino)methyl)benzoic acid; D001565:Benzoates; D001713:Biphenyl Compounds; D006845:Hydrocarbons, Fluorinated; D020030:Nitric Oxide Donors; D014665:Vasodilator Agents; D009599:Nitroprusside; D010656:Phenylephrine; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D006162:Guanylate Cyclase; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester