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Angiotensin and Mineralocorticoid Receptor Antagonism Combined Improves Urinary 8‐Isoprostane Excretion in Ang II‐Infused Rats
Author(s) -
Conte Debra A,
Minas Jacqueline N.,
Aguil Jennifer,
Nishiyama Akira,
Ortiz Rudy M.
Publication year - 2011
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.25.1_supplement.848.8
Subject(s) - endocrinology , antagonism , mineralocorticoid receptor , medicine , mineralocorticoid , excretion , angiotensin ii , urinary system , chemistry , isoprostane , renin–angiotensin system , angiotensin ii receptor type 1 , receptor , pharmacology , blood pressure , oxidative stress , lipid peroxidation
Aldosterone and angiotensin II (AII) promote cardiovascular damage via increased oxidative stress. Mineralocorticoid receptor (MR) antagonism offers cardioprotection against oxidative damage despite increasing intra‐cardiac aldosterone during angiotensin II (AII) dependent hypertension. However, the combined benefits of AT1 and MR blockade on cardiac aldosterone and oxidative/nitrositive stress has not been well described. To examine these effects we studied five groups of Sprague‐Dawley rats: 1) control, 2) AII infused (80 ng/min × 28 d), 3) AII + ARB (10 mg losartan/d × 21d), 4) AII + MR antagonist (25 mg eplerenone/d × 21d) and 5) AII + ARB + MR antagonist. AII increased systolic blood pressure (SBP) 141% of control (117 ± 6.2 mmHg), ARB and co‐therapy returned SBP to control levels, and MR antagonism had no effect. MR antagonism increased plasma (40 ± 6 vs Ctl: 0.8 ± 0.3 pM) and heart (15.8 ± 1.4 vs Ctl 3.6 ± 0.3 pM) aldosterone. MR antagonism reduced heart nitrotyrosine by 52% and ARB by 64% of control, but co‐therapy had further benefit. ARB decreased 8‐isoprostane by 41% and MR antagonism by 52% of control; however, co‐therapy reduced 8‐iso by 78% of control. This data suggests that despite the elevated plasma and heart aldosterone levels, blockade of MR and AII receptors are sufficient to abate the oxidative/nitrositive stress markers usually associated with oxidative damage. Funded by NIH 9T37MD001480