Estrogen modulation of baroreflex function in conscious mice

Pamidimukkala, Jaya; Taylor, Julia A.; Welshons, Wade V.; Lubahn, Dennis B.; Hay, Meredith

doi:10.1152/ajpregu.00761.2001

Cited by 36 publications

(50 citation statements)

References 51 publications

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“…In male subjects, Ang II produces a significantly lower reflex inhibition of HR when compared with the response induced by PE administration, whereas, in females, PE and Ang II exert similar bradycardic baroreflex responses. 8,9,14 In the present study, using MF1 GDX mice of the FCG mouse model, we have shown that Ang II infusion in GDX-XY male mice, when compared with PE response, induces a blunted bradycardic response, whereas GDX-XX female, GDX-XX male, and GDX-XY female mice show the same bradycardic baroreflex response to both PE and Ang II. Mice with XX-SCC but with different gonadal sex (GDX-XX male and GDX-XX female mice) show the same bradycardic baroreflex response.…”

Section: Discussionsupporting

confidence: 55%

“…Moreover, they showed that estrogen replacement in ovariectomized female mice facilitates equally both bradycardic baroreflex response to Ang II and PE administration. 9 A facilitatory role of testosterone in PE bradycardic response in male gonadectomized rats has also been reported. 10 Although previous studies have addressed gonadal steroid modulatory action on the baroreflex control of HR, classic hormonal manipulations have failed to cause sex reversal of the Ang II-bradycardic baroreflex response.…”

mentioning

confidence: 86%

“…The acute administration of Ang II in normotensive male and female patients induces increases in blood pressure (BP) of similar magnitude; however, in men, bradycardic baroreflex response is blunted relative to that observed in women. 8 Likewise, studies carried out by Pamidimukkala et al 9 have shown that, in intact male mice, the slope of Ang II-induced baroreflex bradycardia is significantly less than that evoked by phenylephrine (PE), whereas no differences are observed in the response to both pressor agents in gonadectomized female mice. Moreover, they showed that estrogen replacement in ovariectomized female mice facilitates equally both bradycardic baroreflex response to Ang II and PE administration.…”

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confidence: 99%

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Sex Chromosome Complement Contributes to Sex Differences in Bradycardic Baroreflex Response

et al. 2011

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Abstract-To investigate whether sex chromosome complement modulates bradycardic baroreflex response and contributes to the angiotensin II-bradycardic baroreflex sex differences, we used the four core genotype mouse model in which the effect of gonadal sex and sex chromosome complement is dissociated, allowing comparisons of sexually dimorphic traits among XX and XY females, as well as in XX and XY males. In conscious gonadectomized (GDX) MF1 transgenic mice we evaluated baroreflex regulation of heart rate in response to changes in blood pressure evoked by phenylephrine (1 mg/mL), angiotensin II (100 g/mL), and sodium nitroprusside (1 mg/mL). The administration of phenylephrine in GDX-XY females resulted in a significantly lower baroreflex response when compared with the other genotypes (in beats ⅐ min Ϫ1 ⅐ mm Hg Ϫ1 [slopes of regression lines for GDX-XY females Ϫ3.56Ϯ0.37 versus Ϫ6.06Ϯ0.38, Ϫ6.37Ϯ0.54 and Ϫ6.70Ϯ0.34 for GDX-XY male, GDX-XX female, and GDX-XX male mice, respectively]) {F(1,19)ϭ9.63; PϽ0.01}. In addition, in both GDX-XY males and females, the angiotensin II-bradycardic baroreflex response was attenuated when compared with heart rate changes in GDX-XX male and female mice (in beats ⅐ min Ϫ1 ⅐ mm Hg Ϫ1 [slopes of regression lines: Ϫ2.83Ϯ0.28 versus Ϫ5.76Ϯ0.26 in GDX-XY and GDX-XX mice, respectively]) {F(1,19)ϭ13.91; PϽ0.005}. In contrast, reflex tachycardic responses to sodium nitroprusside were comparable in all of the genotypes. These data support the hypothesis that sex chromosome complement modulates reflex inhibition of heart rate to phenylephrine and angiotensin II. Elucidating the foundational sources of sexually dimorphic traits in the regulation of baroreceptor reflex may enable the design of more appropriate sex-tailored therapeutic treatments in the future.

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Section: Discussionsupporting

confidence: 55%

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confidence: 86%

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confidence: 99%

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Sex Chromosome Complement Contributes to Sex Differences in Bradycardic Baroreflex Response

et al. 2011

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“…A diminished baroreflex and, therefore, a reduced HR variability have also been shown to be independent risk factors for sudden death after myocardial infarction (8). Recently, estrogen was found to augment the slope of the baroreflex bradycardia response to phenylephrine and angiotensin II, supporting previous studies that suggested it modulates baroreflex control of autonomic function (9).…”

Section: T Here Has Been Much Interest In the Cardiovascularsupporting

confidence: 55%

“…This study is the first to demonstrate that deletion of the aromatase gene results in impaired baroreflex regulation of HR. Other studies have documented the effects of estrogen and testosterone on the baroreflex activity of intact and ovariectomized mice and rats (9,36,37). Estrogen significantly increased the slope of the baroreflex bradycardic response to phenylephrine and angiotensin II, but not to sodium nitroprusside, in ovariectomized mice.…”

Section: Discussionmentioning

confidence: 98%

Aromatase-Deficient (ArKO) Mice Have Reduced Blood Pressure and Baroreflex Sensitivity

Head

Obeyesekere

Jones³

et al. 2004

Endocrinology

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Aromatase-deficient (ArKO) mice are deficient in estrogens due to deletion of the aromatase gene. We hypothesized that there may be changes in the cardiovascular system of ArKO mice because of evidence linking estrogens with improved cardiovascular outcomes and the induction of the glucocorticoid-metabolizing enzyme, 11␤-hydroxysteroid dehydrogenase type 2 (11␤HSD2), gene in the kidney, which is important for the regulation of blood pressure (BP). BP and baroreflex sensitivity (BRS) in female conscious ArKO mice were compared with those in age-and weight-matched wild-type (WT) mice. Power spectral analysis was used to determine cardiovascular variability and BRS. Although systolic BP was similar in the two groups, diastolic and mean BPs were lower in the ArKO mice (؊6.3 ؎ 1.9 and ؊4.6 ؎ 2.1 mm Hg, respectively).Heart rate (HR) was greater in the ArKO mice (؉36 ؎ 6 beats/ min). The mean BP in WT mice was 105 mm Hg, and the HR was 481 beats/min. In the autonomic frequency range, BP variability was 74% greater, and HR variability was only 26% that in WT mice. The BRS of ArKO mice was 46% of the value observed in WT mice. 11␤HSD2 levels were unaltered in ArKO mice, except in the kidney, where they were only 10% of WT levels. Estradiol administration to ArKO mice restored renal 11␤HSD2 to WT levels. The results show that ArKO mice have lower diastolic BP, but increased BP variability, perhaps due to an impaired BRS. Thus, aromatase activity is critical for normal autonomic control of the heart and, hence, for reducing the deleterious effects of high BP variability. (Endocrinology 145: 4286 -4291, 2004)

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Endocrine‐Autonomic Linkages

Sladek

Michelini

Stachenfeld

et al. 2015

Comprehensive Physiology

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Interaction between the autonomic nervous system and the neuroendocrine system is critical for maintenance of homeostasis in a wide variety of physiological parameters such as body temperature, fluid and electrolyte balance, and blood pressure and volume. The anatomical and physiological mechanisms underlying integration of the neuroendocrine and autonomic mechanisms responsible for eliciting integrated autonomic and neuroendocrine actions are the focus of this article. This includes a focus on the hypothalamic paraventricular nucleus, because it includes both neuroendocrine neurons and preganglionic autonomic neurons that regulate sympathetic and parasympathetic outflow. The "wired" and "nonwired" mechanisms within PVN that facilitate communication between these neuronal populations are described. The impact of peripheral hormones, specifically the adrenal and gonadal steroids, on the neuroendocrine and autonomic systems is discussed, and exercise is used as a specific example of a physiological challenge/stress that requires precise integration of neuroendocrine and autonomic responses to maintain cardiovascular, fluid, and energy homeostasis.

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Estrogen modulation of baroreflex function in conscious mice

Cited by 36 publications

References 51 publications

Sex Chromosome Complement Contributes to Sex Differences in Bradycardic Baroreflex Response

Sex Chromosome Complement Contributes to Sex Differences in Bradycardic Baroreflex Response

Aromatase-Deficient (ArKO) Mice Have Reduced Blood Pressure and Baroreflex Sensitivity

Endocrine‐Autonomic Linkages

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