Central Inhibition of Tumor Necrosis Factor Alpha Reduces Hypertension by Attenuating Oxidative Stress in the Rostral Ventrolateral Medulla in Renovascular Hypertensive Rats

摘要

Inflammation in the central nervous system is being considered a key player linked to neurogenic hypertension. Using combined in vivo and in vitro approaches, we investigated the effects of central inhibition of TNF-α on blood pressure, sympathetic tone, baroreflex sensitivity, and oxidative stress in the rostral ventrolateral medulla (RVLM) of rats with 2-kidney-1-clip (2K1C) renovascular hypertension. Continuous infusion of pentoxifylline, a TNF-α inhibitor, into the lateral ventricle of the brain for 14 consecutive days reduced blood pressure and improved baroreflex sensitivity in renovascular hypertensive rats. Furthermore, central TNF-α inhibition reduced sympathetic modulation and blunted the increased superoxide accumulation in the RVLM of 2K1C rats. Our findings suggest that TNF-α play an important role in the maintenance of sympathetic vasomotor tone and increased oxidative stress in the RVLM during renovascular hypertension.