Antenatal Hypoxia Induces Programming of Reduced Arterial Blood Pressure Response in Female Rat Offspring: Role of Ovarian Function

Xiao, Daliao; Huang, Xiaohui; Qin, Xue; Zhang, Li

doi:10.1371/journal.pone.0098743

Cited by 13 publications

(21 citation statements)

References 44 publications

(67 reference statements)

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“…A sex-specific effect was also found by Fox et al (122) who demonstrated that renal ANG levels were increased only in male offspring of nicotine-exposed mice, and by Chiossi et al (75) who demonstrated increased carotid artery constriction to ANG II primarily in male offspring of eNOS knockout mice. This sex difference was also observed in the development of hypertension in response to ANG II treatment, which was observed only in male and not female offspring of hypoxic (441) or RUPP (292) pregnancies, an effect which could be also observed in females following ovariectomy. It seems likely, therefore, that the RAS is partly protected in female offspring of compromised pregnancies and might mediate aspects of the cardioprotection observed in some models of developmental programming of cardiovascular disease.…”

Section: Vasoconstrictor Mechanismsmentioning

confidence: 58%

“…Interestingly, Xiao and co-workers (441,443) found a protective effect of estrogen in the programming of ANG II pathways whereby pressor responses to ANG II were increased in males but decreased in females, with the female effect being reversed by ovariectomy. A sex-specific effect was also found by Fox et al (122) who demonstrated that renal ANG levels were increased only in male offspring of nicotine-exposed mice, and by Chiossi et al (75) who demonstrated increased carotid artery constriction to ANG II primarily in male offspring of eNOS knockout mice.…”

Section: Vasoconstrictor Mechanismsmentioning

confidence: 99%

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In Utero Origins of Hypertension: Mechanisms and Targets for Therapy

Morton

Cooke

Davidge³

2016

Physiological Reviews

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The developmental origins of health and disease theory is based on evidence that a suboptimal environment during fetal and neonatal development can significantly impact the evolution of adult-onset disease. Abundant evidence exists that a compromised prenatal (and early postnatal) environment leads to an increased risk of hypertension later in life. Hypertension is a silent, chronic, and progressive disease defined by elevated blood pressure (>140/90 mmHg) and is strongly correlated with cardiovascular morbidity/mortality. The pathophysiological mechanisms, however, are complex and poorly understood, and hypertension continues to be one of the most resilient health problems in modern society. Research into the programming of hypertension has proposed pharmacological treatment strategies to reverse and/or prevent disease. In addition, modifications to the lifestyle of pregnant women might impart far-reaching benefits to the health of their children. As more information is discovered, more successful management of hypertension can be expected to follow; however, while pregnancy complications such as fetal growth restriction, preeclampsia, preterm birth, etc., continue to occur, their offspring will be at increased risk for hypertension. This article reviews the current knowledge surrounding the developmental origins of hypertension, with a focus on mechanistic pathways and targets for therapeutic and pharmacologic interventions.

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Section: Vasoconstrictor Mechanismsmentioning

confidence: 58%

Section: Vasoconstrictor Mechanismsmentioning

confidence: 99%

In Utero Origins of Hypertension: Mechanisms and Targets for Therapy

Morton

Cooke

Davidge³

2016

Physiological Reviews

View full text Add to dashboard Cite

show abstract

“…There were 6 groups of experimental animals: normoxia-sham, hypoxia-sham, normoxia-OVX, hypoxia-OVX, normoxia-OVX+E 2 , and hypoxia-OVX+E 2 . Our recent study [26] in the same animal model demonstrated that plasma estrogen levels were significantly lower in OVX rats (4 pg/ml) than those in sham rats (28 pg/ml), and E 2 replacement restored plasma estrogen levels in OVX rats (32 pg/ml). In addition, plasma estrogen levels were not significantly different between antenatal hypoxic-treated and normoxic control animals [26].…”

Section: Ovariectomy and Estrogen Replacementmentioning

confidence: 75%

“…Ovariectomy (OVX) and sham operation were performed in 8-week-old female rats, as previously described [25][26][27]. Briefly, animals were anesthetized with i.m.…”

Section: Ovariectomy and Estrogen Replacementmentioning

confidence: 99%

“…The sham operation had a ventral midline incision, and ovaries were visualized but not removed. Seven days after OVX, 17β-estradiol (E 2 ) valerate minipellets (7.5 mg for 90-day release, Innovative Research of American) were implanted in half of animals for estrogen replacement, as reported previously [25][26][27]. There were 6 groups of experimental animals: normoxia-sham, hypoxia-sham, normoxia-OVX, hypoxia-OVX, normoxia-OVX+E 2 , and hypoxia-OVX+E 2 .…”

Section: Ovariectomy and Estrogen Replacementmentioning

confidence: 99%

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Estrogen Regulates Angiotensin II Receptor Expression Patterns and Protects the Heart from Ischemic Injury in Female Rats1

Qin

Xiao

Zhang

2015

Biology of Reproduction

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Previous studies have shown that female offspring are resistant to fetal stress-induced programming of ischemic-sensitive phenotype in the heart; however, the mechanisms responsible remain unclear. The present study tested the hypothesis that estrogen plays a role in protecting females in fetal programming of increased heart vulnerability. Pregnant rats were divided into normoxic and hypoxic (10.5% O2 from Day 15 to 21 of gestation) groups. Ovariectomy (OVX) and estrogen (E2) replacement were performed in 8-wk-old female offspring. Hearts of 4-mo-old females were subjected to ischemia and reperfusion injury in a Langendorff preparation. OVX significantly decreased postischemic recovery of left ventricular function and increased myocardial infarction, and no difference was observed between normoxic and hypoxic groups. The effect of OVX was rescued by E2 replacement. OVX decreased the binding of glucocorticoid receptor (GR) to glucocorticoid response elements at angiotensin II type 1 (Agtr1) and type 2 (Agtr2) receptor promoters, resulting in a decrease in Agtr1 and an increase in Agtr2 in the heart. Additionally, OVX decreased estrogen receptor (ER) expression in the heart and inhibited ER/GR interaction in binding to glucocorticoid response elements at the promoters. Consistent with the changes in Agtrs, OVX significantly decreased Prkce abundance in the heart. These OVX-induced changes were abrogated by E2 replacement. The results indicate that estrogen is not directly responsible for the sex dimorphism in fetal programming of heart ischemic vulnerability but suggest a novel mechanism of estrogen in regulating cardiac Agtr1/Agtr2 expression patterns and protecting female hearts against ischemia and reperfusion injury.

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Mechanisms of Sex Disparities in Cardiovascular Function and Remodeling

Chaudhari

Cushen

Osikoya

et al. 2018

Comprehensive Physiology

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Epidemiological studies demonstrate disparities between men and women in cardiovascular disease prevalence, clinical symptoms, treatments, and outcomes. Enrollment of women in clinical trials is lower than men, and experimental studies investigating molecular mechanisms and efficacy of certain therapeutics in cardiovascular disease have been primarily conducted in male animals. These practices bias data interpretation and limit the implication of research findings in female clinical populations. This review will focus on the biological origins of sex differences in cardiovascular physiology, health, and disease, with an emphasis on the sex hormones, estrogen and testosterone. First, we will briefly discuss epidemiological evidence of sex disparities in cardiovascular disease prevalence and clinical manifestation. Second, we will describe studies suggesting sexual dimorphism in normal cardiovascular function from fetal life to older age. Third, we will summarize and critically discuss the current literature regarding the molecular mechanisms underlying the effects of estrogens and androgens on cardiac and vascular physiology and the contribution of these hormones to sex differences in cardiovascular disease. Fourth, we will present cardiovascular disease risk factors that are positively associated with the female sex, and thus, contributing to increased cardiovascular risk in women. We conclude that inclusion of both men and women in the investigation of the role of estrogens and androgens in cardiovascular physiology will advance our understanding of the mechanisms underlying sex differences in cardiovascular disease. In addition, investigating the role of sex‐specific factors in the development of cardiovascular disease will reduce sex and gender disparities in the treatment and diagnosis of cardiovascular disease. © 2019 American Physiological Society. Compr Physiol 9:375‐411, 2019.

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Antenatal Hypoxia Induces Programming of Reduced Arterial Blood Pressure Response in Female Rat Offspring: Role of Ovarian Function

Cited by 13 publications

References 44 publications

In Utero Origins of Hypertension: Mechanisms and Targets for Therapy

In Utero Origins of Hypertension: Mechanisms and Targets for Therapy

Estrogen Regulates Angiotensin II Receptor Expression Patterns and Protects the Heart from Ischemic Injury in Female Rats1

Mechanisms of Sex Disparities in Cardiovascular Function and Remodeling

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