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Oxidative Stress and Angiotensin Receptor Expression in Heart Failure
Author(s) -
Liu Dongmei,
Gao Lie,
Talbitzer Kaye,
Zucker Irving H.
Publication year - 2008
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.22.1_supplement.951.2
Subject(s) - ap 1 transcription factor , angiotensin ii , medicine , receptor , endocrinology , oxidative stress , angiotensin ii receptor type 1 , chemistry , mapk/erk pathway , renin–angiotensin system , activator (genetics) , angiotensin receptor , signal transduction , transcription factor , biochemistry , gene , blood pressure
Angiotensin type I receptors (AT1R) and Angiotensin type II receptors (AT2R) have been shown to counteract each other in physiological and pathological states. However, it is not clear if ROS regulates Ang II receptor protein. The present study investigated if oxidants can regulate the expression of angiotensin receptors in the RVLM of CHF rabbits, and their relationship to the JNK/MAPK pathway and to the transcription factor activator protein 1(AP1). CHF rabbits were randomly divided into two groups. One group (n=5) was treated with intracerebroventricular (ICV) Tempol, the other group was treated with ICV vehicle (n=5). Compared to vehicle treated CHF rabbits Tempol significantly decreased AT1R mRNA expression (1.0 ± 0.16 vs. 0.54 ± 0.05, P<0.05) and AT1R protein expression (1.6 ± 0.29 vs. 0.88 ± 0.16, P<0.05); phosphorylated Jnk protein (0.10 ± 0.02 vs. 0.31 ± 0.10, P<0.05); and phosphorylated c‐Jun (0.14 ± 0.05 vs. 0.02 ± 0.001, P<0.05). Interestingly, compared to the vehicle treated group Tempol up regulated AT2R mRNA expression (1.0 ± 0.1 vs. 1.7 ± 0.16, P<0.01) and protein expression (0.11 ± 0.06 vs. 0.63 ± 0.20, P<0.05) in RVLM of CHF rabbits. These data suggest antioxidant agents may be beneficial in CHF by down regulating AT1R expression and up regulating AT2R. The down stream pathway for AT1R regulation may be through JNK/MAPK and AP1.