Vascular Damage in Resistant Hypertension: TNF-Alpha Inhibition Effects on Endothelial Cells.
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-α and arterial stiffness (pulse wave velocity-PWV) in 32 RHTN and 19 normotensive subjects. Moreover, we investigated the effect of TNF-α inhibition on human endothelial cells (HUVECs) incubated with serum from RHTN and normotensive subjects. HUVECs containing serum obtained from normotensive (n = 8) and hypertensive (n = 8) individuals were treated with TNF-α inhibitor (infliximab). Cell suspensions were used for measurement of DNA fragmentation and reactive oxygen species (ROS) content. RHTN patients showed higher levels of TNF-α compared to normotensive subjects, as well as higher PWV. Positive correlation was found between TNF-α levels 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-α might mediate, at least in part, vascular damage in resistant hypertension.
Laboratory of Cardiovascular Pharmacology, Faculty of Medical Sciences, University of Campinas, 13084971 Campinas, SP, Brazil.
Natália Ruggeri
NR
Barbaro
Department of Pharmacology, Faculty of Medical Sciences, University of Campinas, 13084971 Campinas, SP, Brazil.
Thiago Matos
TM
de Araújo
Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, 14049900 Ribeirao Preto, SP, Brazil.
José Eduardo
JE
Tanus-Santos
Department of Pharmacology, Faculty of Medical Sciences, University of Campinas, 13084971 Campinas, SP, Brazil.
Gabriel Forato
GF
Anhê
Laboratory of Cardiovascular Pharmacology, Faculty of Medical Sciences, University of Campinas, 13084971 Campinas, SP, Brazil.
Vanessa
V
Fontana
Laboratory of Cardiovascular Pharmacology, Faculty of Medical Sciences, University of Campinas, 13084971 Campinas, SP, Brazil.
Heitor
H
Moreno
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D003329:Coronary Vasospasm / Q000453:epidemiology / Q000503:physiopathology*; D003430:Cross-Sectional Studies; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000503:physiopathology*; D000069285:Infliximab / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D063177:Pulse Wave Analysis; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab