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Characterization of the cardiac renin angiotensin system in oophorectomized and estrogen-replete mRen2.Lewis rats.
PLoS One. 2013; 8(10):e76992.Plos

Abstract

The cardioprotective effects of estrogen are well recognized, but the mechanisms remain poorly understood. Accumulating evidence suggests that the local cardiac renin-angiotensin system (RAS) is involved in the development and progression of cardiac hypertrophy, remodeling, and heart failure. Estrogen attenuates the effects of an activated circulating RAS; however, its role in regulating the cardiac RAS is unclear. Bilateral oophorectomy (OVX; n = 17) or sham-operation (Sham; n = 13) was performed in 4-week-old, female mRen2.Lewis rats. At 11 weeks of age, the rats were randomized and received either 17 β-estradiol (E2, 36 µg/pellet, 60-day release, n = 8) or vehicle (OVX-V, n = 9) for 4 weeks. The rats were sacrificed, and blood and hearts were used to determine protein and/or gene expression of circulating and tissue RAS components. E2 treatment minimized the rise in circulating angiotensin (Ang) II and aldosterone produced by loss of ovarian estrogens. Chronic E2 also attenuated OVX-associated increases in cardiac Ang II, Ang-(1-7) content, chymase gene expression, and mast cell number. Neither OVX nor OVX+E2 altered cardiac expression or activity of renin, angiotensinogen, angiotensin-converting enzyme (ACE), and Ang II type 1 receptor (AT1R). E2 treatment in OVX rats significantly decreased gene expression of MMP-9, ACE2, and Ang-(1-7) mas receptor, in comparison to sham-operated and OVX littermates. E2 treatment appears to inhibit upsurges in cardiac Ang II expression in the OVX-mRen2 rat, possibly by reducing chymase-dependent Ang II formation. Further studies are warranted to determine whether an E2-mediated reduction in cardiac chymase directly contributes to this response in OVX rats.

Authors+Show Affiliations

Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

24204720

Citation

Wang, Hao, et al. "Characterization of the Cardiac Renin Angiotensin System in Oophorectomized and Estrogen-replete mRen2.Lewis Rats." PloS One, vol. 8, no. 10, 2013, pp. e76992.
Wang H, Jessup JA, Zhao Z, et al. Characterization of the cardiac renin angiotensin system in oophorectomized and estrogen-replete mRen2.Lewis rats. PLoS One. 2013;8(10):e76992.
Wang, H., Jessup, J. A., Zhao, Z., Da Silva, J., Lin, M., MacNamara, L. M., Ahmad, S., Chappell, M. C., Ferrario, C. M., & Groban, L. (2013). Characterization of the cardiac renin angiotensin system in oophorectomized and estrogen-replete mRen2.Lewis rats. PloS One, 8(10), e76992. https://doi.org/10.1371/journal.pone.0076992
Wang H, et al. Characterization of the Cardiac Renin Angiotensin System in Oophorectomized and Estrogen-replete mRen2.Lewis Rats. PLoS One. 2013;8(10):e76992. PubMed PMID: 24204720.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Characterization of the cardiac renin angiotensin system in oophorectomized and estrogen-replete mRen2.Lewis rats. AU - Wang,Hao, AU - Jessup,Jewell A, AU - Zhao,Zhuo, AU - Da Silva,Jaqueline, AU - Lin,Marina, AU - MacNamara,Lindsay M, AU - Ahmad,Sarfaraz, AU - Chappell,Mark C, AU - Ferrario,Carlos M, AU - Groban,Leanne, Y1 - 2013/10/25/ PY - 2013/06/19/received PY - 2013/08/28/accepted PY - 2013/11/9/entrez PY - 2013/11/10/pubmed PY - 2014/8/27/medline SP - e76992 EP - e76992 JF - PloS one JO - PLoS One VL - 8 IS - 10 N2 - The cardioprotective effects of estrogen are well recognized, but the mechanisms remain poorly understood. Accumulating evidence suggests that the local cardiac renin-angiotensin system (RAS) is involved in the development and progression of cardiac hypertrophy, remodeling, and heart failure. Estrogen attenuates the effects of an activated circulating RAS; however, its role in regulating the cardiac RAS is unclear. Bilateral oophorectomy (OVX; n = 17) or sham-operation (Sham; n = 13) was performed in 4-week-old, female mRen2.Lewis rats. At 11 weeks of age, the rats were randomized and received either 17 β-estradiol (E2, 36 µg/pellet, 60-day release, n = 8) or vehicle (OVX-V, n = 9) for 4 weeks. The rats were sacrificed, and blood and hearts were used to determine protein and/or gene expression of circulating and tissue RAS components. E2 treatment minimized the rise in circulating angiotensin (Ang) II and aldosterone produced by loss of ovarian estrogens. Chronic E2 also attenuated OVX-associated increases in cardiac Ang II, Ang-(1-7) content, chymase gene expression, and mast cell number. Neither OVX nor OVX+E2 altered cardiac expression or activity of renin, angiotensinogen, angiotensin-converting enzyme (ACE), and Ang II type 1 receptor (AT1R). E2 treatment in OVX rats significantly decreased gene expression of MMP-9, ACE2, and Ang-(1-7) mas receptor, in comparison to sham-operated and OVX littermates. E2 treatment appears to inhibit upsurges in cardiac Ang II expression in the OVX-mRen2 rat, possibly by reducing chymase-dependent Ang II formation. Further studies are warranted to determine whether an E2-mediated reduction in cardiac chymase directly contributes to this response in OVX rats. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/24204720/Characterization_of_the_cardiac_renin_angiotensin_system_in_oophorectomized_and_estrogen_replete_mRen2_Lewis_rats_ L2 - https://dx.plos.org/10.1371/journal.pone.0076992 DB - PRIME DP - Unbound Medicine ER -