title: Phosphate binding reduces aortic angiotensin-converting enzyme and enhances nitric oxide bioactivity in experimental renal insufficiency.
abstract: BACKGROUND
  Disturbed calcium-phosphorus metabolism is associated with increased kidney angiotensin-converting enzyme (ACE) in experimental chronic renal insufficiency (CRI). However, information about the effects of phosphate binding and loading on vascular ACE is lacking.
  
  
  METHODS
  Fifteen weeks after 5/6 nephrectomy (NX), rats were placed on a phosphate-binding (NX+Ca, 3.0% Ca), phosphate-loading (NX+Pi, 1.5% Pi), or control diet for 12 weeks (NX and sham).
  
  
  RESULTS
  Aortic ACE, blood pressure, plasma phosphate, and parathyroid hormone were increased in the NX and NX+Pi groups, but were reduced with phosphate binding. Endothelium-mediated relaxations of isolated mesenteric conduit artery rings to acetylcholine were impaired in the NX and NX+Pi groups, but did not differ from sham in NX+Ca rats. Experiments with nitric oxide (NO) synthase inhibition in vitro suggested that the NO-mediated component of acetylcholine response was lower in the NX and NX+Pi groups, but did not differ from sham in NX+Ca rats. In all NX groups, aortic endothelial NO synthase (eNOS) was reduced, while plasma and urine concentrations of NO metabolites were increased. Aortic nitrated proteins and calcification were increased in the NX and NX+Pi groups when compared with the NX+Ca and sham groups.
  
  
  CONCLUSIONS
  Hypertension in the NX model of CRI was associated with reduced vasorelaxation, decreased eNOS, and increased ACE and nitrated proteins in the aorta. Phosphate binding with calcium carbonate enhanced vasorelaxation via endogenous NO and suppressed elevation of ACE and nitrated proteins, suggesting reduced vascular oxidative stress. Our findings support the view that correction of the calcium-phosphorus balance prevents CRI-induced vascular pathophysiology.
authors.affiliation: School of Medicine, University of Tampere, Tampere, Finland.
authors.forename: Arttu
authors.initials: A
authors.lastname: Eräranta
authors.forename: Suvi
authors.initials: S
authors.lastname: Törmänen
authors.forename: Peeter
authors.initials: P
authors.lastname: Kööbi
authors.forename: Tuija I
authors.initials: TI
authors.lastname: Vehmas
authors.forename: Päivi
authors.initials: P
authors.lastname: Lakkisto
authors.forename: Ilkka
authors.initials: I
authors.lastname: Tikkanen
authors.forename: Eeva
authors.initials: E
authors.lastname: Moilanen
authors.forename: Onni
authors.initials: O
authors.lastname: Niemelä
authors.forename: Jukka
authors.initials: J
authors.lastname: Mustonen
authors.forename: Ilkka
authors.initials: I
authors.lastname: Pörsti
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000201:enzymology*; D001018:Aortic Diseases; D001794:Blood Pressure; D002114:Calcinosis; D002119:Calcium Carbonate / Q000008:administration & dosage; D004727:Endothelium / Q000503:physiopathology; D008638:Mesenteric Arteries / Q000502:physiology; D009392:Nephrectomy; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D018384:Oxidative Stress; D010281:Parathyroid Hormone / Q000097:blood; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D010710:Phosphates / Q000008:administration & dosage / Q000097:blood*; D051381:Rats; D051436:Renal Insufficiency, Chronic / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D010281:Parathyroid Hormone; D010710:Phosphates; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D007703:Peptidyl-Dipeptidase A; D002119:Calcium Carbonate; D000109:Acetylcholine; D009638:Norepinephrine