title: Impaired coronary endothelial function in a rat model of spontaneous albuminuria.
abstract: BACKGROUND
  Albuminuria is an independent risk factor of coronary artery disease and has been proposed to reflect a general endothelial disorder. The Munich Wistar Frömter (MWF) rat strain develops spontaneous albuminuria and, therefore, may be an interesting experimental model to study alterations of endothelial function under conditions of increased albuminuria. Our aim was to investigate if the MWF strain shows generalized endothelial dysfunction or endothelial dysfunction localized to the coronary vascular bed, and if so, determine which endothelial dilative mediators are involved.
  
  
  METHODS
  Coronary and mesenteric arteries were investigated for endothelium-dependent relaxation and the contribution of prostacyclin, nitric oxide (NO) and endothelium-dependent hyperpolarization (EDH) in MWF rats compared to normal Wistar rats. In addition, as MWF rats show increased blood pressure, spontaneously hypertensive rats (SHR) with similar hypertension but without increased albuminuria also were studied.
  
  
  RESULTS
  Maximal total endothelium-dependent relaxation of coronary arteries was strongly impaired in MWF rats (55 +/- 3%) compared to Wistar (89 +/- 5%) and SHR (89 +/- 2%) P < 0.05, respectively. The NO-mediated relaxation as well as the relaxation mediated by EDH were significantly lower in coronary arteries from MWF compared to Wistar. In mesenteric arteries of MWF the endothelium-dependent relaxation was intact.
  
  
  CONCLUSIONS
  The strong impairment of coronary endothelium-dependent relaxation in the MWF model of spontaneous albuminuria may be due to defects in production or activity of NO and EDH. The intact mesenteric endothelium-dependent relaxation suggests that increased albuminuria may not be related to generalized endothelial vasodilator dysfunction in this model. Selective impairment of coronary endothelial function in a setting of spontaneous albuminuria may be a feature of the MWF that may be employed to further study cause-effect relations between albuminuria and coronary artery disease.
authors.affiliation: Department of Clinical Pharmacology, Division of Nephrology, University of Groningen, Groningen, The Netherlands.
authors.forename: Simone
authors.initials: S
authors.lastname: Gschwend
authors.forename: Sara-Joan
authors.initials: SJ
authors.lastname: Pinto-Sietsma
authors.forename: Hendrik
authors.initials: H
authors.lastname: Buikema
authors.forename: Yigal M
authors.initials: YM
authors.lastname: Pinto
authors.forename: Wiek H
authors.initials: WH
authors.lastname: van Gilst
authors.forename: Angela
authors.initials: A
authors.lastname: Schulz
authors.forename: Dick
authors.initials: D
authors.lastname: de Zeeuw
authors.forename: Reinhold
authors.initials: R
authors.lastname: Kreutz
mesh_terms: D000419:Albuminuria / Q000503:physiopathology*; D000818:Animals; D001685:Biological Factors / Q000502:physiology; D003331:Coronary Vessels / Q000503:physiopathology*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000503:physiopathology*; D008638:Mesenteric Arteries / Q000503:physiopathology; D009569:Nitric Oxide / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar
chemical_list: D001685:Biological Factors; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide