Cardiovascular Research Advance Access first published online on May 10, 2008
This version [Corrected Proof] published online on May 29, 2008
Cardiovascular Research, doi:10.1093/cvr/cvn119
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Cross-talk between cytokines and renin–angiotensin in hypothalamic paraventricular nucleus in heart failure: role of nuclear factor-
B
1 Shanxi Medical University, Taiyuan 030001, People's Republic of China
2 Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA
* Corresponding author. Tel: +1 225 578 9752 (J.F.)/+1 225 578 9550 (Y.-M.K.); fax: +1 225 578 9895(J.F.)/+1 225 578 9895 (Y.-M.K.). E-mail address: jfrancis{at}lsu.edu (J.F.)/ymkang{at}lsu.edu (Y.-M.K.)
Aims: Nuclear factor-kappa B (NF-
B) is a potent inducer of pro-inflammatory cytokines (PIC) and oxidative stress in cardiovascular disease. In this study, we determined whether upregulation of NF-B in the hypothalamic paraventricular nucleus (PVN) contributed to neurohumoral excitation either directly, or via interaction with the renin–angiotensin system (RAS), in heart failure (HF).
Methods and results: Rats were implanted with intracerebroventricular (ICV) cannulae and subjected to coronary artery ligation, or sham surgery (SHAM). Subsequently, animals were ICV treated with the angiotensin type 1 receptor (AT1-R) antagonist losartan (LOS, 20 µg/h), or SN50 (2 µg/h), which inhibits nuclear translocation of NF-B, or tempol (TEMP, 80 µg/h), a membrane-permeable superoxide scavenger, or vehicle for 4 weeks. HF induced a significant increase in the expression of AT1-R, PIC, and NAD(P)H oxidase genes and NF-B p50 in the PVN and in plasma norepinephrine (NE) levels when compared with SHAM rats. In contrast, ICV LOS, SN50, or TEMP attenuated PIC, NF-B p50, AT1-R and NAD(P)H oxidase genes in the PVN compared with vehicle-treated HF rats. Treatment with LOS, SN50, or TEMP also reduced plasma levels of NE, angiotensin II, and PIC, and decreased left ventricular end diastolic pressure.
Conclusion: These findings indicate that NF-B mediates the cross-talk between RAS and PIC in the PVN in HF, and that superoxide stimulates more NF-B in the PVN and contributes to neurohumoral excitation.
KEYWORDS NF-B; Heart failure; Brain; Angiotensin; Superoxide
Time for primary review: 30 days
Both authors contributed equally to this study.