Testosterone Facilitates the Baroreceptor Control of Reflex Bradycardia: Role of Cardiac Sympathetic and Parasympathetic Components

El‐Mas, Mahmoud M.; Afify, Elham A.; El-Din, Mahmoud M. Mohy; Omar, Abdelsattar M.; Sharabi, Fouad M.

doi:10.1097/00005344-200111000-00012

Cited by 81 publications

(85 citation statements)

References 26 publications

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“…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: 95%

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

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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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Section: Discussionmentioning

confidence: 95%

“…Thus, the lack of estrogen in ArKO mice may explain the reduced baroreflex sensitivity. In contrast, the higher levels of testosterone would be expected to increase the baroreflex gain according to studies in conscious rats (36) that suggests that in the ArKO mice, the effect of a lack of estrogen predominates.…”

Section: Discussionmentioning

confidence: 99%

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

Head

Obeyesekere

Jones³

et al. 2004

Endocrinology

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“…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.…”

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confidence: 99%

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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“…Physical activity, mental stress, and sexual steroids are factors known to affect autonomic function in the adult, but how these factors exert their influence in children is not known. [7][8][9][10] It seems reasonable to assume that the efficiency of autonomic neural integration increases from infancy to young adulthood, but this assumption needs to be tested, its mechanism determined, and the time course of changes defined. Autonomic function data obtained from healthy children might serve as reference values for autonomic studies performed on young patients with cardiovascular disease.…”

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confidence: 99%

Maturation of Cardiovagal Autonomic Function From Childhood to Young Adult Age

et al. 2004

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Background-Cardiovagal autonomic control declines with age in adult subjects, which is related in part to increasing stiffness of the barosensory vessel wall. It is not known, however, whether autonomic function changes with age in children. Methods and Results-We studied 137 healthy subjects divided into 4 age groups: group 1, 7 to 14 years; group 2, 11 to 14 years; group 3, 15 to 18 years; and group 4, 19 to 22 years. Brachial artery pressure was measured by sphygmomanometry and continuous radial artery pressure and carotid artery pulse pressure (⌬P) by applanation tonometry. The R-R interval was derived from the ECG. Autonomic function was assessed by spontaneous sequence and frequency-domain indices, which indicate the extent of coupling between fluctuations in heart rate and systolic pressure. Carotid artery diastolic diameter (DD) and pulsatile distension (⌬D) were measured by echo wall tracking; carotid compliance coefficient (CC) was defined as ⌬D/⌬P and distensibility coefficient as 2⌬D/DD · ⌬P. , with no significant changes afterward. CC and DC were inversely proportional to age (rϭϪ0.49 and Ϫ0.62, respectively, PϽ0.001). The efficiency of neural integrative mechanisms, estimated as the ratio of spontaneous indices and CC, more than doubled from group 1 to group 3. Spontaneous indices were linearly related to measures of cardiac vagal activity. Conclusions-The increase in spontaneous indices from early childhood to adolescence, despite gradual stiffening of the carotid artery, may indicate improved cardiovagal autonomic function, which is most likely a result of maturation of neural mechanisms, attaining peak level at adolescence.

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Testosterone Facilitates the Baroreceptor Control of Reflex Bradycardia: Role of Cardiac Sympathetic and Parasympathetic Components

Cited by 81 publications

References 26 publications

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

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

Sex Chromosome Complement Contributes to Sex Differences in Bradycardic Baroreflex Response

Maturation of Cardiovagal Autonomic Function From Childhood to Young Adult Age

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