Abstract 1754: Central Nervous System Blockade of Tumor Necrosis Factor Attenuates Angiotensin II Induced Hypertension
Background: A growing body of evidence indicates an interaction between renin angiotensin system and proinflammatory cytokines (PIC) in cardiovascular disease. In this study, we explored whether the hypertension induced by angiotensin II (AngII) is due to increased production of PIC and oxidative stress genes in the paraventricular nucleus (PVN) of the hypothalamus, the vital cardiovascular regulatory center of the brain.
Methods: Adult male Sprague-Dawley rats were implanted with radio telemetry transmitters to measure blood pressure, and subjected to intracerebroventricular (ICV) infusion of etanercept (10 μg/kg/day) and/or subcutaneous infusion of AngII (200 ng/kg/min) for 4 weeks. Rats that received vehicle were used as controls. At the end of the study, rats were sacrificed, the brain and heart were removed for the measurement of PIC, oxidative stress genes in the PVN and left ventricle (LV) by real time PCR.
Results: (see table⇓) AngII infusion resulted in a significant increase in the blood pressure, cardiac hypertrophy with increased production of PIC and oxidative stress genes in the PVN and LV. ICV treatment with etanercept significantly decreased the AngII induced effect on blood pressure. In addition, etanercept treatment resulted in a significant attenuation of cardiac hypertrophy as indicated by decreased heart weight to body weight ratio when compared with AngII infused rats. Etanercept treatment also decreased expression of TNF and IL-6 in the LV and PVN of AngII treated rats.
Conclusions: These observations indicate that central blockade of TNF in the brain protects rats against AngII dependant hypertension and cardiac hypertrophy by down regulating PIC and oxidative stress genes in the PVN.