Angiotensin II type 1 receptor (AT1-R) and
nuclear factor-kappaB (NF-κB) in the paraventricular nucleus (PVN) play important roles in
heart failure (HF); however, the central mechanisms by which AT1-R and NF-κB contribute to sympathoexcitation in HF are yet unclear. In this study, we determined whether interaction between AT1-R and NF-κB in the PVN modulates
neurotransmitters and contributes to
NAD(P)H oxidase-dependent oxidative stress and sympathoexcitation in HF. Rats were implanted with bilateral PVN
cannulae and subjected to coronary artery
ligation or
sham surgery (
SHAM). Subsequently, animals were treated for 4 weeks through bilateral PVN infusion with either vehicle or
losartan (LOS, 10 μg/h), an AT1-R antagonist; or
pyrrolidine dithiocarbamate (
PDTC, 5 μg/h), a NF-κB inhibitor via osmotic minipump.
Myocardial infarction (MI) rats had higher levels of
glutamate (Glu),
norepinephrine (NE) and NF-κB p65 activity, lower levels of
gamma-aminobutyric acid (
GABA), and more positive neurons for phosphorylated IKKβ and gp91(
phox) (a subunit of
NAD(P)H oxidase) in the PVN when compared to
SHAM rats. MI rats also had higher levels of renal sympathetic nerve activity (RSNA) and plasma proinflammatory
cytokines (PICs), NE and
epinephrine. PVN infusions of LOS or
PDTC attenuated the decreases in
GABA and the increases in gp91(
phox), NF-κB activity, Glu and NE, in the PVN of HF rats. PVN infusions of LOS or
PDTC also attenuated the increases in RSNA and plasma PICs, NE and
epinephrine in MI rats. These findings suggest that interaction between AT1 receptor and NF-κB in the PVN contributes to oxidative stress and sympathoexcitation by modulating
neurotransmitters in
heart failure.