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

Alynne Carvalho-Galvão; Drielle D Guimarães; José L De Brito Alves; Valdir A Braga

doi:10.3389/fphys.2019.00491

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

Front Physiol. 2019 Apr 30:10:491. doi: 10.3389/fphys.2019.00491. eCollection 2019.

Authors

Alynne Carvalho-Galvão¹, Drielle D Guimarães^{1

2}, José L De Brito Alves³, Valdir A Braga^{1

2}

Affiliations

¹ Biotechnology Center, Federal University of Paraíba, João Pessoa, Brazil.
² Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
³ Department of Nutrition, Health Sciences Center, Federal University of Paraíba, João Pessoa, Brazil.

Abstract

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.

Keywords: TNF-α; baroreflex; proinflammatory cytokines; renovascular hypertension; superoxide; sympathetic nervous system.