Gender‐Specific Regulation of Cardiovascular Function: Estrogen as Key Player

Huang, An; Kaley, Gabor

doi:10.1080/10739680490266162

Cited by 97 publications

(87 citation statements)

References 330 publications

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“…Elevated myogenic responses in males compared with females has been demonstrated in rat gracilis muscle (21) and mouse cerebral (11), rat coronary (26), and mouse mesenteric (53) arteries. The presence of estrogen in females may reduce myogenic responses in an endothelial nitric oxide synthase-dependent manner (11,19,45). In contrast, we found that mesenteric arteries from 4-mo-old female C offspring exhibited significantly greater myogenic responses than those from age-matched male C offspring, with the differences resolved by 7 mo of age.…”

Section: Discussioncontrasting

confidence: 56%

“…Although it is not surprising that each gender was affected differently by a particular in utero insult simply based on hormonal differences (19,39), it is particularly interesting that the vascular effects for each gender differed depending on the insult. These gender-specific changes could be directly due to differences in sensitivity and adaptation to the specific insult while still in utero, or females may have greater vascular compensatory mechanisms after birth.…”

Section: Discussionmentioning

confidence: 99%

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Increased myogenic tone in 7-month-old adult male but not female offspring from rat dams exposed to hypoxia during pregnancy

Hemmings¹,

Williams²,

Davidge³

2005

American Journal of Physiology-Heart and Circulatory Physiology

100

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Hemmings, D. G., S. J. Williams, and S. T. Davidge. Increased myogenic tone in 7-month-old adult male but not female offspring from rat dams exposed to hypoxia during pregnancy. Am J Physiol Heart Circ Physiol 289: H674 -H682, 2005. First published April 15, 2005; doi:10.1152/ajpheart.00191.2005.-Intrauterine growth restriction (IUGR) increases the risk of cardiovascular disease later in life. Vascular dysfunction occurs in adult offspring from animal models of IUGR including maternal undernutrition, but the influence of reduced fetal oxygen supply on adult vascular function is unclear. Myogenic responses, essential for vascular tone regulation, have not been evaluated in these offspring. We hypothesized that 7-mo-old offspring from hypoxic (12% O 2; H) or nutrient-restricted (40% of control; NR) rat dams would show greater myogenic responses than their 4-mo-old littermates or control (C) offspring through impaired modulation by vasodilators. Growth restriction occurred in male H (P Ͻ 0.01), male NR (P Ͻ 0.01), and female NR (P Ͻ 0.02), but not female H, offspring. Myogenic responses in mesenteric arteries from males but not females were increased at 7 mo in H (P Ͻ 0.01) and NR (P Ͻ 0.05) vs. C offspring. There was less modulation of myogenic responses after inhibition of nitric oxide synthase (P Ͻ 0.05), prostaglandin H synthase (P Ͻ 0.005), or both enzymes (P Ͻ 0.001) in arteries from 7-mo male H vs. C offspring. Thus reduced vasodilator modulation may explain elevated myogenic responses in 7-mo male H offspring. In contrast, there was increased modulation of myogenic responses in arteries from 7-mo female H vs. C or NR offspring after inhibition of both enzymes (P Ͻ 0.05). Thus increased vasodilator modulation may maintain myogenic responses in female H offspring at control levels. In summary, vascular responses in adult offspring from adverse intrauterine environments are impaired in a genderspecific, age-dependent, and maternal insult-dependent manner, with males more profoundly affected. fetal programming; undernutrition; nitric oxide; vascular function; gender EPIDEMIOLOGIC STUDIES SUGGEST that intrauterine growth-restricted infants are at increased risk of developing hypertension and other cardiovascular diseases in adult life (1). Fetal adaptations to an adverse intrauterine environment may include altered cellular differentiation and tissue growth to ensure short-term survival but may also lead to impaired cardiovascular and endocrine function later in adult life (1). Intrauterine growth restriction, in many cases, is thought to occur as a result of placental dysfunction leading to impaired oxygen and/or nutrient transfer to the fetus. Experimentally, undernutrition during pregnancy (2,6,10,18,28,32,40) or fetal exposure to elevated glucocorticoid levels (35, 36, 38) results in vascular dysfunction in adult offspring. However, the long-term effects of prenatal hypoxia are unclear.Exposure to chronic hypoxia in ovo results in reduced nitric oxide modulation of vascular responses in arteries from both e...

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Section: Discussioncontrasting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Increased myogenic tone in 7-month-old adult male but not female offspring from rat dams exposed to hypoxia during pregnancy

Hemmings¹,

Williams²,

Davidge³

2005

American Journal of Physiology-Heart and Circulatory Physiology

100

View full text Add to dashboard Cite

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“…In a subsequent set of experiments we tested whether this is due to a protective effect of estrogen, as suggested for many cardiac derangements (18). Ovariectomized female rats were made diabetic 3 wk after surgery.…”

Section: Gender Differences In Conductionmentioning

confidence: 99%

“…gap junctions; connexin43 CARDIOVASCULAR DISEASE IS a leading cause of mortality in the Western world (17). Significant sex differences exist in the incidence and outcomes of cardiovascular derangements (26) and in normal and pathological cardiac function (14,18,46). Electrical dysfunction manifests as diverse arrhythmias, some of which result from changes in ionic currents underlying the cardiac action potential (30).…”

mentioning

confidence: 99%

Sex-dependent impairment of cardiac action potential conduction in type 1 diabetic rats

Shimoni¹,

Emmett²,

Schmidt³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

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The incidence of diabetes mellitus is increasing. Cardiac dysfunction often develops, resulting in diverse arrhythmias. These arise from ion channel remodeling or from altered speed and pattern of impulse propagation. Few studies have investigated impulse propagation in the diabetic heart. We previously showed a reduced conduction reserve in the diabetic heart, with associated changes in intercellular gap junctions. The present study investigated whether these effects are sex specific. Hearts from control and streptozotocin-diabetic male and female rats were used. Optical mapping was performed with the voltage-sensitive dye di-4-ANEPPS, using Langendorff-perfused hearts. Isolated ventricular cells and tissue sections were used for immunofluorescent labeling of the gap junction protein connexin43 (Cx43). The gap junction uncoupler heptanol (0.75 mM) or elevated K+ (9 mM, to reduce cell excitability) produced significantly greater slowing of propagation in diabetic males than females. In ovariectomized diabetic females, 9 mM K+ slowed conduction significantly more than in nonovariectomized females. The subcellular redistribution (lateralization) of the gap junction protein Cx43 was smaller in diabetic females. Pretreatment of diabetic males with the angiotensin-converting enzyme inhibitor quinapril reduced Cx43 lateralization and the effects of 9 mM K+ on propagation. In conclusion, the slowing of cardiac impulse propagation in type 1 diabetes is smaller in female rats, partly due to the presence of female sex hormones. This difference is (partly) mediated by sex differences in activation of the cardiac renin-angiotensin system.

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“…Crucial roles for ERα in the protection against vascular injury, activation of endothelial NO synthase (NOS) and anti-atherosclerotic effects have been amply documented (28,29). Genetic deletion of ERß results in the development of hypertension in middle-aged female and male mice due to multiple abnormalities of ion channel function in blood vessels (30).…”

Section: The Role Of Sex Hormones and Their Central Receptors In Angimentioning

confidence: 99%

Sex differences in angiotensin II- induced hypertension

Xue¹,

Johnson²,

Hay³

2007

Braz J Med Biol Res

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Sex differences in the development of hypertension and cardiovascular disease have been described in humans and in animal models. In this paper we will review some of our studies which have as their emphasis the examination of the role of sex differences and sex steroids in modulating the central actions of angiotensin II (ANG II) via interactions with free radicals and nitric oxide, generating pathways within brain circumventricular organs and in central sympathomodulatory systems. Our studies indicate that low-dose infusions of ANG II result in hypertension in wild-type male mice but not in intact wild-type females. Furthermore, we have demonstrated that ANG IIinduced hypertension in males is blocked by central infusions of the androgen receptor antagonist, flutamide, and by central infusions of the superoxide dismutase mimetic, tempol. We have also found that, in comparison to females, males show greater levels of intracellular reactive oxygen species in circumventricular organ neurons following long-term ANG II infusions. In female mice, ovariectomy, central blockade of estrogen receptors or total knockout of estrogen α receptors augments the pressor effects of ANG II. Finally, in females but not in males, central blockade of nitric oxide synthase increases the pressor effects of ANG II. Taken together, these results suggest that sex differences and estrogen and testosterone play important roles in the development of ANG II-induced hypertension.

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Gender‐Specific Regulation of Cardiovascular Function: Estrogen as Key Player

Cited by 97 publications

References 330 publications

Increased myogenic tone in 7-month-old adult male but not female offspring from rat dams exposed to hypoxia during pregnancy

Increased myogenic tone in 7-month-old adult male but not female offspring from rat dams exposed to hypoxia during pregnancy

Sex-dependent impairment of cardiac action potential conduction in type 1 diabetic rats

Sex differences in angiotensin II- induced hypertension

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