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Angiotensin II and mineralocorticoid receptor antagonism decrease cardiac nitrotyrosine content and recover glutathione peroxidase activity in Angiotensin II‐infused rats (856.10)
Author(s) -
Minas Jacqueline,
Thorwald Max,
Conte Debra,
VázquezMedina JosePablo,
Nishiyama Akira,
Ortiz Rudy
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.856.10
Subject(s) - medicine , endocrinology , mineralocorticoid receptor , angiotensin ii , losartan , angiotensin ii receptor type 1 , aldosterone , oxidative stress , eplerenone , chemistry , angiotensin receptor , nitrotyrosine , glutathione peroxidase , candesartan , receptor , superoxide dismutase , nitric oxide , nitric oxide synthase
Angiotensin II (Ang II) and aldosterone (aldo) contribute to cardiovascular damage via oxidative stress, but their respective contributions remain elusive. To independently assess the contributions of Ang II and aldo during Ang II‐dependent hypertension, five groups of Sprague Dawley rats (n =11‐14/group) were studied: 1) Control, 2) Ang II infused (80 ng/min x 28d), 3) Ang II + angiotensin receptor blocker (ARB; 10 mg losartan/kg/d x 21d), 4) Ang II + mineralocorticoid receptor antagonist (Epl; 100 mg eplerenone/d x 21d), and 5) Ang II + ARB + Epl (Combo). ARB and Combo reduced the 65% Ang II‐induced increase in systolic blood pressure (SBP), but Epl had no effect. Epl exacerbated the increase in plasma and heart aldo while ARB reduced both. Ang II increased relative heart mass 19% and heart cardiotrophin‐1 content 57%. All treatments prevented these increases. Ang II reduced mean glutathione peroxidase activity 29%, while ARB and Combo recovered levels beyond Control by 25 and 28%, respectively. Ang II also increased superoxide dismutase (SOD) activity 20% whereas all treatments reduced SOD. Ang II increased mean heart nitrotyrosine (NT) content 3‐fold and mean 4‐hydroxynonenal (HNE) content 26%. All treatments improved NT, but Epl had no effect on HNE levels. Despite the inability to reduce SBP, chronic MR blockade prevented oxidative stress suggesting aldo as a therapeutic target for AT1‐mediated oxidative damage. Grant Funding Source : Supported in parts by: NHLBI K02HL103787/R01HL091767, NIH NIMHD T37MD001480, NIH