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Adult Male Offspring of Polycystic Ovary Syndrome (PCOS) Rat Model Have Exaggerated Pressor Response to Low Dose Angiotensin (Ang) II
Author(s) -
Shawky Noha,
Reckelhoff Jane
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.01575
Subject(s) - offspring , polycystic ovary , medicine , endocrinology , testosterone (patch) , anovulation , blood pressure , diabetes mellitus , biology , insulin resistance , pregnancy , genetics
Background Polycystic Ovary Syndrome (PCOS), the most common endocrine disorder in women of reproductive age, is characterized by hyperandrogenemia, oligo‐/anovulation, polycystic ovaries and elevated blood pressure (BP). Because the guidelines for diagnosis of PCOS have only been in place since 2003‐4, it is unclear as to whether hypertension/cardiovascular disease (CVD) develops in adult offspring of PCOS women. Using a well‐characterized model of PCOS, the hyperandrogenemic female (HAF) rat, that develops most of the characteristics of PCOS (including hypertension), the current study tested the hypothesis that male HAF offspring have an exaggerated pressor response to angiotensin (Ang) II, while female HAF offspring do not. Methods : The HAF model was induced in Sprague Dawley (SD) females by implantation of 5α‐dihydrotestosterone pellets (DHT; 7.5 mg/90 days, s.c.) starting at 4 weeks (wks) of age throughout life. HAF rats (at 10‐12 wks of age) were mated with SD males, and allowed to deliver and lactate. Male and female offspring (F 1 HAF ) were left untreated (e.g. no DHT). Control dams were implanted with placebo pellets (q 90 days), mated and allowed to lactate their pups (F 1 Contr. ). At 4‐6 months (mos) of age, both male and female F 1 HAF and F 1 Contr. rats were implanted with radiotelemetry transmitters to measure their BP (3‐4 rats/group; 1 rat/litter/group). Following recovery for 2 wks, baseline mean arterial pressure (MAP) was measured for 7 days; then enalapril (25 mg/kg/d in drinking water) was given to all rats for 9 days. After blocking endogenous Ang II biosynthesis, enalapril‐treated rats were implanted with minipumps to deliver Ang II (50 ng/kg/min, s.c. = low dose) for 18 days, while continuing enalapril. Minipumps were then replaced to increase the Ang II dose (200 ng/kg/min, s.c.) for 5 days, while continuing enalapril. Results Panel A : At baseline (B), MAP was similar in all groups and enalapril ( E ) significantly decreased MAP to similar levels in all groups. Panel B : Ang II infusion (low dose) significantly increased MAP in male F 1 HAF ,compared to male F 1 contr . There was a tendency for low dose Ang II to increase MAP in female F 1 contr but not in female F 1 HAF. Panel C : High dose Ang II increasedMAP further but to a greater extent in male F 1 contr and F 1 HAF than in females. Conclusion These results indicate that male offspring of HAF dams have enhanced pressor sensitivity to low dose Ang II, but the differences are masked by the higher dose of Ang II. These data suggest that men whose mothers had PCOS during pregnancy may be at greater risk of CVD.