BLOOD PRESSURE LOWERING EFFECTS OF CENTRAL TNF-α BLOCKADE DEPENDS ON FUNCTIONAL LEPTIN SIGNALING

Background: Obesity is a major independent risk factor for the development and progression of arterial hypertension. Leptin-mediated sympathoexcitation is a common phenomenon in obesity. Since leptin leads to the synthesis of Tumor Necrosis Factor (TNF)-alpha in the central nervous system, we hypothesized that the pathological activation of the sympathetic nervous system in obesity-associated hypertension may be mediated by central leptin-related TNF-alpha mechanisms. Material and methods: We compared the long-term effects of TNF-alpha inhibition on mean arterial blood pressure, heart rate, baroreflex sensitivity and sympathetic tone in animals with a functional leptin signaling (i.e. lean Zucker rats - LZR) and in animals insensitive to leptin (i.e. obese Zucker rats - OZR). Results: central inhibition of TNF-alpha in normotensive LZR significantly lowered mean arterial blood pressure, decreased sympathetic activity and improved baroreflex sensitivity but not in the OZR group. Conclusions: These findings suggest that a functionally central leptin-TNF-alpha signaling plays a key role in mediating the central sympathetic outflow and may represent a promising approach to ameliorate the pathophysiology of obesity related-hypertension.