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Title: SRC-1 regulates blood pressure and aortic stiffness in female mice

Author
item HINTON, ANTENTOR - Children'S Nutrition Research Center (CNRC)
item YANG, YONGJIE - Children'S Nutrition Research Center (CNRC)
item QUICK, ANN - Baylor College Of Medicine
item XU, PINGWEN - Children'S Nutrition Research Center (CNRC)
item REDDY, CHITRA - Baylor College Of Medicine
item YAN, XIAOFENG - Children'S Nutrition Research Center (CNRC)
item REYNOLDS, COREY - Baylor College Of Medicine
item TONG, QINGCHUN - University Of Texas Health Science Center
item ZHU, LIANGRU - Children'S Nutrition Research Center (CNRC)
item XU, JIANMING - Baylor College Of Medicine
item WEHRENS, XANDER - Baylor College Of Medicine
item XU, YONG - Children'S Nutrition Research Center (CNRC)
item REDDY, ANILKUMAR - Baylor College Of Medicine

Submitted to: PLOS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/5/2016
Publication Date: 12/22/2016
Citation: Hinton, A.O., Yang, Y., Quick, A.P., Xu, P., Reddy, C.L., Yan, X., Reynolds, C.L., Tong, Q., Zhu, L., Xu, J., Wehrens, X.H., Xu, Y., Reddy, A.K. 2016. SRC-1 regulates blood pressure and aortic stiffness in female mice. PLoS One. 11(12):e0168644.

Interpretive Summary: Hypertension is a serious global health problem and treatments are not ideal. Here we showed that mice lacking SRC-1, a molecule in cells, show increased blood pressure. These findings suggested that SRC-1 could be a potential target for treatment of hypertension.

Technical 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.