Vascular Damage in Resistant Hypertension: TNF-Alpha Inhibition Effects on Endothelial Cells

Abstract

Inflammatory cytokines have been associated with the pathophysiology of hypertension and target organ damage (TOD). Resistant hypertensive patients (RHTN) are characterized by poor blood pressure control and higher prevalence of TOD. This study evaluated the relationship between plasma levels of TNF-αand arterial stiffness (pulse wave velocity—PWV) in 32 RHTN and 19 normotensive subjects. Moreover, we investigated the effect of TNF-αinhibition on human endothelial cells (HUVECs) incubated with serum from RHTN and normotensive subjects. HUVECs containing serum obtained from normotensiven=8and hypertensiven=8individuals were treated with TNF-αinhibitor (infliximab). Cell suspensions were used for measurement of DNA fragmentation and reactive oxygen species (ROS) content. RHTN patients showed higher levels of TNF-αcompared to normotensive subjects, as well as higher PWV. Positive correlation was found between TNF-αlevels and PWV measures in the whole group. HUVECs incubated with serum from RHTN showed increased cell apoptosis and higher ROS content compared to normotensive subjects. Infliximab attenuated the apoptosis of HUVECs incubated with serum from RHTN, but no effect in ROS production was observed. Our findings suggest that TNF-αmight mediate, at least in part, vascular damage in resistant hypertension.