Abstract 5941: Bilateral Blockade of NF-kB in the Paraventricular Nucleus Attenuates Angiotensin II-Induced Blood Pressure Response
A growing body of evidence suggests that inflammatory mediators contribute to the pathogenesis of cardiovascular disease. Findings from our lab indicate that proinflammatory cytokines and their transcription factor, nuclear transcription factor kappa B (NFkB), are increased in the hypothalamic paraventricular nucleus (PVN) and contribute to hypertension. In this study, we determined whether chronic NFkB blockade in the PVN can modulate blood pressure response.
Methods: Male Sprague-Dawley rats were implanted with a telemetry probe for continuous monitoring of blood pressure and a bilateral cannula for chronic infusion of drugs into the PVN. Subsequently, rats were implanted subcutaneously with osmotic minipumps containing ANGII (200 ng/kg/min); NFkB decoy (2μg/kg), or scrambled NFkB decoy, was given into the PVN chronically also using osmotic minipumps. At the end of the 14 day study, the PVN was micro-punched for the measurement of gene expression for renin angiotensin system (RAS) and oxidative stress components using real time RT-PCR for mRNA and immunohistochemistry for protein analysis. Superoxide, total reactive oxygen species and peroxynitrite in the PVN was measured using electron paramagnetic resonance spectroscopy.
Results are tabulated. Bilateral NFkB blockade prevented the ANGII-induced increase in blood pressure compared to the scrambled decoy treated ANGII group. This was accompanied by decreases in the activation of RAS genes and oxidative stress. These finding suggest that ANGII infusion increases NFkB in the PVN and contributes to blood pressure response.
Conclusion: Inflammatory mediators in the PVN interact with RAS components, increase oxidative stress and contribute to hypertension.