TY - JOUR
T1 - Cardiovascular-renal and metabolic characterization of a rat model of polycystic ovary syndrome
AU - Yanes, Licy L.
AU - Romero, Damian G.
AU - Moulana, Mohaddetheh
AU - Lima, Roberta
AU - Davis, Deborah D.
AU - Zhang, Huimin
AU - Lockhart, Rachel
AU - Racusen, Lorraine C.
AU - Reckelhoff, Jane F.
N1 - Funding Information:
The authors acknowledge the support of the National Institutes of Health RO1s HL66072 and HL69194 and PO1 HL51971 (to JFR), and the American Heart Association Scientific Development Award #0830239N (to LLY). L.L. Yanes designed the experiments analyzed the data, and helped write the manuscript; D.G. Romero performed all real-time polymerase chain reactions; M. Moulana performed the cholesterol studies; R. Lima performed the metabolism cage and telemetry studies; D.D. Davis implanted telemeters and performed the kidney function studies; H. Zhang performed all sex steroid assays, protein assays, and nitrate/nitrite assays; R. Lockhart performed daily maintenance of rats, daily vaginal smearing, and body weights; L.C. Racusen was the renal pathologist; and J.F. Reckelhoff was the principal investigator and wrote the manuscript. The authors have indicated that they have no conflicts of interest regarding the content of this article.
PY - 2011/4
Y1 - 2011/4
N2 - 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, p22phox, p47phox, gp91phox, 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.
AB - 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, p22phox, p47phox, gp91phox, 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.
KW - angiotensinogen
KW - cholesterol
KW - insulin resistance
KW - leptin
KW - oxidative stress
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U2 - 10.1016/j.genm.2010.11.013
DO - 10.1016/j.genm.2010.11.013
M3 - Article
C2 - 21536229
AN - SCOPUS:79955592340
SN - 1550-8579
VL - 8
SP - 103
EP - 115
JO - Gender Medicine
JF - Gender Medicine
IS - 2
ER -