title: Characterization of the cardiac renin angiotensin system in oophorectomized and estrogen-replete mRen2.Lewis rats.
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.affiliation: Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Jewell A
authors.initials: JA
authors.lastname: Jessup
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Zhao
authors.forename: Jaqueline
authors.initials: J
authors.lastname: Da Silva
authors.forename: Marina
authors.initials: M
authors.lastname: Lin
authors.forename: Lindsay M
authors.initials: LM
authors.lastname: MacNamara
authors.forename: Sarfaraz
authors.initials: S
authors.lastname: Ahmad
authors.forename: Mark C
authors.initials: MC
authors.lastname: Chappell
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Ferrario
authors.forename: Leanne
authors.initials: L
authors.lastname: Groban
mesh_terms: D000803:Angiotensin I / Q000378:metabolism; D000808:Angiotensinogen / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D053818:Chymases / Q000235:genetics / Q000378:metabolism; D004958:Estradiol / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D004967:Estrogens / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007150:Immunohistochemistry; D008407:Mast Cells / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D010052:Ovariectomy; D010446:Peptide Fragments / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D011917:Rats, Inbred Lew; D055647:Rats, Transgenic; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D012083:Renin / Q000235:genetics / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D004967:Estrogens; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D044140:Receptor, Angiotensin, Type 1; D043562:Receptors, G-Protein-Coupled; C473112:Ren2 protein, mouse; D000808:Angiotensinogen; D004958:Estradiol; D000803:Angiotensin I; D053818:Chymases; D012083:Renin; D020780:Matrix Metalloproteinase 9; C118790:angiotensin I (1-7)