title: Biopterin status in dogs with myxomatous mitral valve disease is associated with disease severity and cardiovascular risk factors.
abstract: BACKGROUND
  Endothelial dysfunction (ED) has been suggested to be associated with myxomatous mitral valve disease (MMVD) in dogs. Tetrahydrobiopterin (BH4) is an important cofactor for production of the endothelium-derived vasodilator nitric oxide (NO). Under conditions of oxidative stress, BH4 is oxidized to the biologically inactive form dihydrobiopterin (BH2). Thus, plasma concentrations of BH2 and BH4 may reflect ED and oxidative stress.
  
  
  OBJECTIVE
  To determine plasma concentrations of BH2 and BH4 in dogs with different degrees of MMVD.
  
  
  METHODS
  Eighty-four privately owned dogs grouped according to ACVIM guidelines (37 healthy control dogs including 13 Beagles and 24 Cavalier King Charles Spaniels [CKCSs], 33 CKCSs with MMVD of differing severity including 18 CKCSs [group B1] and 15 CKCSs [group B2], and 14 dogs of different breeds with clinical signs of congestive heart failure [CHF] because of MMVD [group C]).
  
  
  METHODS
  Dogs underwent clinical examination including echocardiography. Plasma concentrations of BH2 and BH4 were measured using high-performance liquid chromatography with fluorescence detection.
  
  
  RESULTS
  Higher plasma BH4 and BH2 concentrations were found with dogs in CHF compared with all other groups (control, B1 and B2; P ≤ .001). Females had higher concentrations of BH4 and BH4/BH2 (P ≤ .0003). BH4/BH2 was found to decrease with age (P < .0001). Cardiovascular risk factors in humans such as passive smoking (P ≤ .01) and increased body weight (P ≤ .009) were associated with lower BH4 concentrations.
  
  
  CONCLUSIONS
  Age, sex, body weight, passive smoking, and cardiac status are associated with plasma biopterin concentration in dogs. Additional studies should clarify the clinical implications of the findings.
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.
authors.forename: M J
authors.initials: MJ
authors.lastname: Reimann
authors.forename: J
authors.initials: J
authors.lastname: Häggström
authors.forename: A
authors.initials: A
authors.lastname: Mortensen
authors.forename: J
authors.initials: J
authors.lastname: Lykkesfeldt
authors.forename: J E
authors.initials: JE
authors.lastname: Møller
authors.forename: T
authors.initials: T
authors.lastname: Falk
authors.forename: L H
authors.initials: LH
authors.lastname: Olsen
mesh_terms: D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives* / Q000097:blood; D002318:Cardiovascular Diseases / Q000209:etiology / Q000662:veterinary; D004283:Dog Diseases / Q000097:blood*; D004285:Dogs; D004452:Echocardiography / Q000662:veterinary; D005260:Female; D006349:Heart Valve Diseases / Q000097:blood / Q000662:veterinary*; D008297:Male; D008943:Mitral Valve; D012307:Risk Factors; D012720:Severity of Illness Index; D014028:Tobacco Smoke Pollution
chemical_list: D014028:Tobacco Smoke Pollution; D001708:Biopterins; C017226:7,8-dihydrobiopterin; C003402:sapropterin
keywords: Endothelial dysfunction; Mitral regurgitation; Oxidative stress; Tetrahydrobiopterin