Abstract MP02: Central Tumor Necrosis Factor-alpha Induces Sensitization Of Angiotensin II-elicited Hypertension
Proinflammatory cytokines such as tumor necrosis factor (TNF)-α play an important role in regulating autonomic and cardiovascular function in hypertension. Angiotensin (Ang) II can upregulate proinflammatory cytokine signaling in the brain. Our previous studies using an Induction-Delay-Expression experimental design demonstrated that pretreatment with a subpressor dose of Ang II modifies the brain to produce a sensitized response to a subsequent treatment with a pressor dose of Ang II. The present study tested the hypothesis that brain TNF-α signaling contributes to Ang II-induced sensitization. Male rats were prepared for telemetry recording of BP and were treated during Induction with 1) a peripheral subpressor dose of Ang II (10 ng/kg/min, SC) or 2) peripheral subpressor Ang II plus the TNF-α synthesis inhibitor pentoxifylline (10 μg/h, ICV) or 3) TNF-α (20 ng/d, ICV) for one week. After one week Delay, rats were treated during Expression with Ang II (120 ng/kg/min, SC) for 2 weeks. Rats that received the subpressor Ang II pretreatment responded with enhanced hypertension to Ang II (Δ44.5±3.4 mmHg vs. Δ25.4±2.8 mmHg). Induction with TNF-α or the TNF-α synthesis inhibitor mimicked or abolished sensitization produced by the subpressor dose of ANG II (Δ42.8±5.3 mmHg and Δ28.2±1.9 mmHg), respectively. RT-PCR analysis of tissue from the lamina terminalis indicated that subpressor Ang II or TNF-α given during Induction up-regulated mRNA expression of several renin-angiotensin system components and proinflammatory cytokines including renin, angiotensin converting enzyme, interleukin (IL)-1β and IL-6. The results indicate that Ang II-induced sensitization of Ang II hypertension depends on central proinflammatory cytokine-mediated effects.
Author Disclosures: B. Xue: None. F. Guo: None. Y. Yu: None. T.G. Beltz: None. R.B. Felder: None. A.K. Johnson: None.
- © 2014 by American Heart Association, Inc.