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.
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: Ricardo Azziz; Enrico Carmina; Didier Dewailly; Evanthia Diamanti-Kandarakis; Hector F Escobar-Morreale; Walter Futterweit; Onno E Janssen; Richard S Legro; Robert J Norman; Ann E Taylor; Selma F Witchel Journal: J Clin Endocrinol Metab Date: 2006-08-29 Impact factor: 5.958
Authors: Licy L Yanes; Damian G Romero; Joshua W Iles; Radu Iliescu; Celso Gomez-Sanchez; Jane F Reckelhoff Journal: Am J Physiol Regul Integr Comp Physiol Date: 2006-03-30 Impact factor: 3.619
Authors: Licy Yanes; Damian Romero; Radu Iliescu; Valeria E Cucchiarelli; Lourdes A Fortepiani; Francisco Santacruz; William Bell; Huimin Zhang; Jane F Reckelhoff Journal: Am J Physiol Regul Integr Comp Physiol Date: 2004-12-16 Impact factor: 3.619
Authors: Tracey A Van Kempen; Ankita Narayan; Elizabeth M Waters; Jose Marques-Lopes; Costantino Iadecola; Michael J Glass; Virginia M Pickel; Teresa A Milner Journal: J Comp Neurol Date: 2015-12-23 Impact factor: 3.215
Authors: R Taylor Sawyer; Elizabeth R Flynn; Zachary M Hutchens; Jan M Williams; Michael R Garrett; Christine Maric-Bilkan Journal: Am J Physiol Renal Physiol Date: 2012-07-18
Authors: Noha M Shawky; Chetan N Patil; Carolina Dalmasso; Rodrigo O Maranon; Damian G Romero; Heather Drummond; Jane F Reckelhoff Journal: Hypertension Date: 2020-08-03 Impact factor: 10.190