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Comparative Study
. 2016 Dec 22;11(12):e0168644.
doi: 10.1371/journal.pone.0168644. eCollection 2016.

SRC-1 Regulates Blood Pressure and Aortic Stiffness in Female Mice

Antentor Othrell Hinton Jr  1 , Yongjie Yang  1 , Ann P Quick  2   3 , Pingwen Xu  1 , Chitra L Reddy  4 , Xiaofeng Yan  1 , Corey L Reynolds  2   3   5 , Qingchun Tong  6 , Liangru Zhu  7 , Jianming Xu  8 , Xander H T Wehrens  2   3 , Yong Xu  1   8 , Anilkumar K Reddy  3   9   10
Affiliations
Comparative Study

SRC-1 Regulates Blood Pressure and Aortic Stiffness in Female Mice

Antentor Othrell Hinton Jr et al. PLoS One. .

Abstract

Framingham Heart Study suggests that dysfunction of steroid receptor coactivator-1 may be involved in the development of hypertension. However, there is no functional evidence linking steroid receptor coactivator-1 to the regulation of blood pressure. We used immunohistochemistry to map the expression of steroid receptor coactivator-1 protein in mouse brain, especially in regions implicated in the regulation of blood pressure. Steroid receptor coactivator-1 protein was found in central amygdala, medial amygdala, supraoptic nucleus, arcuate nucleus, ventromedial, dorsomedial, paraventricular hypothalamus, and nucleus of the solitary tract. To determine the effects of steroid receptor coactivator-1 protein on cardiovascular system we measured blood pressures, blood flow velocities, echocardiographic parameters, and aortic input impedance in female steroid receptor coactivator-1 knockout mice and their wild type littermates. Steroid receptor coactivator-1 knockout mice had higher blood pressures and increased aortic stiffness when compared to female wild type littermates. Additionally, the hearts of steroid receptor coactivator-1 knockout mice seem to consume higher energy as evidenced by increased impedance and higher heart rate pressure product when compared to female wild type littermates. Our results demonstrate that steroid receptor coactivator-1 may be functionally involved in the regulation of blood pressure and aortic stiffness through the regulation of sympathetic activation in various neuronal populations.

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Conflict of interest statement

Dr. Xander Wehrens serves as guest editor for PLOS ONE. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials. Regarding employment with commercial entity, Indus Instruments, Dr. Reddy regularly reports any significant financial conflicts to the Department of Medicine at Baylor College of Medicine.

Figures

Fig 1
Fig 1. Expression of SRC-1 in the brain.
Immunofluorescence staining of SRC-1 in various brain regions of WT female mice. 3V, third ventricle; ARC, arcuate nucleus of the hypothalamus; CeA, central amygdala; DMH, dorsal medial nucleus of the hypothalamus; MeA, medial amygdala; NTS, the nucleus of the solitary tract; OPT, optic tract; PVN, paraventricular nucleus of the hypothalamus; Sch, suprachiasmatic nucleus; SON, supraoptic nucleus; VMH, ventromedial nucleus of the hypothalamus (VMH). Scale bars = 100 μm.
Fig 2
Fig 2. Validation of SRC-1-KO mice.
3,3′-diaminobenzidine immunohistochemistry staining for SRC-1 in the medial amygdala of female WT (A) or SRC-1-KO (B) mice. OPT, optic tract; MeA, medial amygdala. Scale bar = 100 μm.
Fig 3
Fig 3. Aortic blood pressure and rate pressure product.
Aortic blood pressure parameters of female WT and SRC-1-KO mice. (A) Systolic blood pressure (SBP), (B) Diastolic blood pressure (DBP), (C) Mean blood pressure (MBP), (D) Pulse pressure, (E) Heart rate, and (F) Rate pressure product (RPP). Data are presented as mean±SEM (n = 5-7/group); *—p< 0.05. The information supporting this figure is in S1 Dataset.
Fig 4
Fig 4. Left ventricular pressure indices.
Left ventricular blood pressure parameters of female WT and SRC-1-KO mice. (A) Peak left ventricular pressure (PLVP), (B) Maximal contractiIity (+dP/dtmax), (C) Maximal relaxation (-dP/dtmax), (D) relaxation time constant (tau), and (E) left ventricular end diastolic pressure (LVEDP) obtained from the left ventricular pressure of the mice. Data are presented as mean±SEM (n = 5-7/group); *—p< 0.05. The information supporting this figure is in S2 Dataset.
Fig 5
Fig 5. Diameter of the aortic arch.
Representative B-mode images of aortic arch in female WT (A) and SRC-1-KO (B) mice. Quantification (C) revealed a decrease in diameter of the aortic arch in SRC-1-KO mice. Data are presented as mean±SEM (n = 4-5/group); *—p< 0.05. The information supporting this figure is in S3 Dataset.
Fig 6
Fig 6. Cardiac flow velocity indices.
Peak aortic outflow velocity (A), peak mitral-E flow velocity (B), peak mitral-A flow velocity (C) and mitral E/A ratio (D) obtained from cardiac Doppler flow velocity signals in female WT and SRC-1-KO mice. Data are presented as mean±SEM (n = 4-6/group); *—p< 0.05. The information supporting this figure is in S4 Dataset.
Fig 7
Fig 7. Loss of SRC-1 in female mice results in aortic stiffness.
Parameters of aortic impedance in female WT and SRC-1-KO mice. Total peripheral resistance, ZP (A), impedance at first harmonic, Z1 (B), characteristic impedance, ZC (C), and impedance based pulse wave velocity, PWVZ (D). Data are presented as mean±SEM (n = 4-6/group); * = p< 0.05. The information supporting this figure is in S5 Dataset.
See this image and copyright information in PMC

References

    1. Sookram C, Munodawafa D, Phori PM, Varenne B, Alisalad A (2015) WHO's supported interventions on salt intake reduction in the sub-Saharan Africa region. Cardiovasc Diagn Ther 5: 186–190. 10.3978/j.issn.2223-3652.2015.04.04 - DOI - PMC - PubMed
    1. World Health Organization Report (2011).
    1. Hajjar I, Kotchen JM, Kotchen TA (2006) Hypertension: trends in prevalence, incidence, and control. Annu Rev Public Health 27: 465–490. 10.1146/annurev.publhealth.27.021405.102132 - DOI - PubMed
    1. Wiinberg N, Hoegholm A, Christensen HR, Bang LE, Mikkelsen KL, Nielsen PE, et al. (1995) 24-h ambulatory blood pressure in 352 normal Danish subjects, related to age and gender. Am J Hypertens 8: 978–986. 10.1016/0895-7061(95)00216-2 - DOI - PubMed
    1. Burt VL, Whelton P, Roccella EJ, Brown C, Cutler JA, Higgins M, et al. (1995) Prevalence of hypertension in the US adult population. Results from the Third National Health and Nutrition Examination Survey, 1988–1991. Hypertension 25: 305–313. - PubMed

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