NF-κB Blockade in Hypothalamic Paraventricular Nucleus Inhibits High-Salt-Induced Hypertension Through NLRP3 and...

Area of Science:

• Neuroscience
• Cardiovascular Physiology
• Molecular Biology

Background:

• High salt intake triggers inflammation and oxidative stress in the hypothalamic paraventricular nucleus (PVN), contributing to salt-sensitive hypertension.
• Nuclear factor-κB (NF-κB) signaling is implicated in this process.

Purpose of the Study:

• To investigate if chronic inhibition of NF-κB in the PVN can delay hypertension progression.
• To determine if NF-κB inhibition upregulates anti-inflammatory cytokines and reduces NLRP3 inflammasome components and oxidative stress markers in the PVN.

Main Methods:

• Dahl salt-sensitive rats were fed a high-salt or normal-salt diet for 6 weeks.
• Rats received bilateral PVN infusions of either vehicle or pyrrolidine dithiocarbamate (PDTC), an NF-κB inhibitor, via osmotic minipump.
• Mean arterial pressure, plasma catecholamines, and PVN molecular markers (p-IKKβ, NF-κB p65, Fra-LI, NOX-4, NLRP3, IL-1β, IL-10) were measured.

Main Results:

• High-salt diet increased mean arterial pressure, plasma norepinephrine and epinephrine, and PVN levels of p-IKKβ, NF-κB p65 activity, Fra-LI, NOX-4, NLRP3, and IL-1β, while decreasing IL-10.
• PVN infusion of PDTC attenuated these high-salt-induced changes, including hypertension and molecular markers of inflammation and oxidative stress.

Conclusions:

• High-salt-induced NF-κB activation in the PVN promotes hypertension via sympathoexcitation, NLRP3 inflammasome activation, and oxidative stress.
• Inhibiting NF-κB in the PVN attenuates these detrimental pathways, thereby mitigating hypertension.