Noha M Shawky1,2,3, Carolina Dalmasso4, Norma B Ojeda5,2,3, Yvonne Zuchowski1,2,3, Nina Stachenfeld6, Barbara T Alexander7,2,3, Jane F Reckelhoff1,2,3. 1. Department of Cell and Molecular Biology. 2. Women's Health Research Center. 3. Mississippi Center of Excellence in Perinatal Research, University of Mississippi Medical Center, Jackson, Mississippi. 4. Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington. 5. Department of Pediatrics. 6. The John Pierce Laboratory, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut. 7. Department of Physiology and Biophysics and.
Abstract
BACKGROUND: Polycystic ovary syndrome (PCOS) is characterized by reproductive and metabolic dysfunction, and elevated blood pressure (BP). The cardiometabolic consequences of maternal hyperandrogenemia on offspring, either as adults or with aging, have not been well studied. We previously found that male offspring of hyperandrogenemic female (HAF) rats, a model of PCOS, are normotensive but have an exaggerated pressor response to angiotensin (Ang) II. METHOD: In this study, the hypothesis was tested that adult and aging female offspring of HAF rats develop a metabolic and hypertensive phenotype. Control and HAF rats were implanted prepubertally with placebo or dihydrotestosterone pellets, which continued throughout pregnancy and lactation. RESULTS: Female offspring of HAF dams had lower birth weight than female control offspring. Although female HAF offspring (aged 16-24 weeks) had no differences in intrarenal Ang II, plasma lipids or proteinuria, they did have lower intrarenal Ang (1-7) and lower nitrate/nitrite excretion than controls. Adult HAF offspring had similar baseline BP as controls, but had an attenuated pressor response to Ang II. With aging (16-20 months), female HAF offspring remained normotensive with an attenuated pressor response to Ang II and high salt diet but more proteinuria and higher intrarenal Ang(1-7) than controls. CONCLUSION: Taken together, these data suggest that female HAF offspring are protected from developing hypertension, but may be at risk for renal injury with aging. Future studies are necessary to determine whether adult and postmenopausal offspring of PCOS women are at increased risk for cardiovascular dysfunction.Graphical abstract:http://links.lww.com/HJH/B820.
BACKGROUND: Polycystic ovary syndrome (PCOS) is characterized by reproductive and metabolic dysfunction, and elevated blood pressure (BP). The cardiometabolic consequences of maternal hyperandrogenemia on offspring, either as adults or with aging, have not been well studied. We previously found that male offspring of hyperandrogenemic female (HAF) rats, a model of PCOS, are normotensive but have an exaggerated pressor response to angiotensin (Ang) II. METHOD: In this study, the hypothesis was tested that adult and aging female offspring of HAF rats develop a metabolic and hypertensive phenotype. Control and HAF rats were implanted prepubertally with placebo or dihydrotestosterone pellets, which continued throughout pregnancy and lactation. RESULTS: Female offspring of HAF dams had lower birth weight than female control offspring. Although female HAF offspring (aged 16-24 weeks) had no differences in intrarenal Ang II, plasma lipids or proteinuria, they did have lower intrarenal Ang (1-7) and lower nitrate/nitrite excretion than controls. Adult HAF offspring had similar baseline BP as controls, but had an attenuated pressor response to Ang II. With aging (16-20 months), female HAF offspring remained normotensive with an attenuated pressor response to Ang II and high salt diet but more proteinuria and higher intrarenal Ang(1-7) than controls. CONCLUSION: Taken together, these data suggest that female HAF offspring are protected from developing hypertension, but may be at risk for renal injury with aging. Future studies are necessary to determine whether adult and postmenopausal offspring of PCOS women are at increased risk for cardiovascular dysfunction.Graphical abstract:http://links.lww.com/HJH/B820.
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