title: Cardiovascular-renal and metabolic characterization of a rat model of polycystic ovary syndrome.
abstract: BACKGROUND
  Polycystic ovary syndrome (PCOS) is the most common reproductive dysfunction in premenopausal women. PCOS is also associated with increased risk of cardiovascular disease when PCOS first occurs and later in life. Hypertension, a common finding in women with PCOS, is a leading risk factor for cardiovascular disease. The mechanisms responsible for hypertension in women with PCOS have not been elucidated.
  
  
  OBJECTIVE
  This study characterized the cardiovascular-renal consequences of hyperandrogenemia in a female rat model.
  
  
  METHODS
  Female Sprague-Dawley rats (aged 4-6 weeks) were implanted with dihydrotestosterone or placebo pellets lasting 90 days. After 10 to 12 weeks, blood pressure (by radiotelemetry), renal function (glomerular filtration rate, morphology, protein, and albumin excretion), metabolic parameters (plasma insulin, glucose, leptin, cholesterol, and oral glucose tolerance test), inflammation (plasma tumor necrosis factor-α), oxidative stress (mRNA expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits, p22(phox), p47(phox), gp91(phox), and NOX4), nitrate/nitrite excretion and mRNA expression of components of the renin-angiotensin system (angiotensinogen, angiotensin-I-converting enzyme [ACE], and AT1 receptor) were determined.
  
  
  RESULTS
  Plasma dihydrotestosterone increased 3-fold in hyperandrogenemic female (HAF) rats, whereas plasma estradiol levels did not differ compared with control females. HAF rats exhibited estrus cycle dysfunction. They also had increased food intake and body weight, increased visceral fat, glomerular filtration rate, renal injury, insulin resistance and metabolic dysfunction, oxidative stress, and increased expression of angiotensinogen and ACE and reduced AT1 receptor expression.
  
  
  CONCLUSIONS
  The HAF rat is a unique model that exhibits many of the characteristics of PCOS in women and is a useful model to study the mechanisms responsible for PCOS-mediated hypertension.
authors.affiliation: Women's Health Research Center, Center of Excellence in Cardiovascular-Renal Research, Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi 39216-4505, USA.
authors.forename: Licy L
authors.initials: LL
authors.lastname: Yanes
authors.forename: Damian G
authors.initials: DG
authors.lastname: Romero
authors.forename: Mohaddetheh
authors.initials: M
authors.lastname: Moulana
authors.forename: Roberta
authors.initials: R
authors.lastname: Lima
authors.forename: Deborah D
authors.initials: DD
authors.lastname: Davis
authors.forename: Huimin
authors.initials: H
authors.lastname: Zhang
authors.forename: Rachel
authors.initials: R
authors.lastname: Lockhart
authors.forename: Lorraine C
authors.initials: LC
authors.lastname: Racusen
authors.forename: Jane F
authors.initials: JF
authors.lastname: Reckelhoff
mesh_terms: D000808:Angiotensinogen / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000209:etiology; D013196:Dihydrotestosterone / Q000097:blood* / Q000378:metabolism; D004195:Disease Models, Animal; D004958:Estradiol / Q000097:blood* / Q000378:metabolism; D005260:Female; D005919:Glomerular Filtration Rate; D005951:Glucose Tolerance Test; D007674:Kidney Diseases / Q000453:epidemiology* / Q000209:etiology; D020738:Leptin / Q000097:blood; D024821:Metabolic Syndrome; D018384:Oxidative Stress; D011085:Polycystic Ovary Syndrome / Q000150:complications*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000502:physiology
chemical_list: D001786:Blood Glucose; D020738:Leptin; D013196:Dihydrotestosterone; D000808:Angiotensinogen; D004958:Estradiol