Angiotensin II induced pro‐inflammatory cytokines and oxidative stress in the brain are attenuated in mice lacking the gene for TNF‐α

Abstract

Angiotensin II (Ang II) has been shown to have both central and peripheral effects. Recent studies suggest a functional crosstalk between angiotensin II and the pro‐inflammatory cytokine (PIC) tumor necrosis factor‐alpha (TNF‐a) in the progression of cardiovascular diseases. Recent findings from our lab suggest that Ang II increases the expression of PICs in the PVN, and that mice lacking the gene for TNF‐a (TNF‐a−/−) have attenuated hypertensive and hypertrophic responses to Ang II infusion. However, the mechanism for this effect is not known. In this study we examined whether Ang II infusion in TNF‐a−/− mice had any effect on PICs and oxidative stress in the hypothalamus and brainstem. Male TNF‐a−/− and control B61295F2/J (WT) mice were subcutaneously implanted with osmotic minipumps containing Ang II (1µg/kg/min) or saline for 14 days. Ang II infusion resulted in increased expression of PICs such as IL‐1beta, IL‐6, and TNF‐α in the hypothalamus and brainstem of WT mice. Ang II infusion also increased the expression of the NOX‐2 subunit of NADPH oxidase, indicating increased oxidative stress. However, this increase in PICs and oxidative stress was attenuated in Ang II infused TNF‐α ‐/− mice. Findings from the present study suggest that brain inflammatory cytokines contributes to the development of Ang II induced hypertension. Grant support: NHLBI grant HL‐80544 for Dr. Joseph Francis.