title: Plasma 8-isoprostane levels are associated with endothelial dysfunction in resistant hypertension.
abstract: BACKGROUND
  Impaired endothelial function and arterial stiffness are associated with hypertension and are important risk factors for cardiovascular events. Reactive oxygen species reduce nitric oxide bioavailability and have a pivotal role in endothelial function. Resistant hypertension (RHTN) is characterized by blood pressure (BP) above goal (140/90mmHg) in spite of the concurrent use of ≥3 antihypertensive drugs of different classes. This study evaluated the association between 8-isoprostane levels, an oxidative stress marker, endothelial function and arterial stiffness, in RHTN.
  
  
  METHODS
  Ninety-four RHTN and 55 well-controlled hypertensive (HT) patients were included. Plasma 8-isoprostane levels were determined by ELISA. Also, flow-mediated dilation (FMD) and pulse wave velocity (PWV) were evaluated to determine endothelial function and arterial stiffness, respectively.
  
  
  RESULTS
  Levels of 8-isoprostane were markedly higher in RHTN compared to HT patients (22.5±11.2 vs. 17.3±9.8pg/ml, p<0.05, respectively). A significant inverse correlation was observed between FMD and 8-isoprostane (r=-0.35, p=0.001) in RHTN. Finally, multiple logistic regression revealed that 8-isoprostane was a significant predictor of endothelial dysfunction (FMD≤median) in RHTN group.
  
  
  CONCLUSIONS
  RHTN showed markedly higher oxidative stress measured by 8-isoprostane, compared to HT patients. Taken together, our findings suggest the involvement of oxidative stress in endothelial function in RHTN.
authors.affiliation: Laboratory of Cardiovascular Pharmacology, Faculty of Medical Sciences, University of Campinas, Campinas, SP, Brazil.
authors.forename: Ana Paula Cabral
authors.initials: AP
authors.lastname: de Faria
authors.affiliation: Laboratory of Cardiovascular Pharmacology, Faculty of Medical Sciences, University of Campinas, Campinas, SP, Brazil.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Fontana
authors.affiliation: Laboratory of Cardiovascular Pharmacology, Faculty of Medical Sciences, University of Campinas, Campinas, SP, Brazil.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Modolo
authors.affiliation: Laboratory of Cardiovascular Pharmacology, Faculty of Medical Sciences, University of Campinas, Campinas, SP, Brazil.
authors.forename: Natália Ruggeri
authors.initials: NR
authors.lastname: Barbaro
authors.affiliation: Laboratory of Cardiovascular Pharmacology, Faculty of Medical Sciences, University of Campinas, Campinas, SP, Brazil.
authors.forename: Andréa Rodrigues
authors.initials: AR
authors.lastname: Sabbatini
authors.affiliation: Laboratory of Cardiovascular Pharmacology, Faculty of Medical Sciences, University of Campinas, Campinas, SP, Brazil.
authors.forename: Isabella Fagian
authors.initials: IF
authors.lastname: Pansani
authors.affiliation: Laboratory of Cardiovascular Pharmacology, Faculty of Medical Sciences, University of Campinas, Campinas, SP, Brazil.
authors.forename: Silvia E
authors.initials: SE
authors.lastname: Ferreira-Melo
authors.affiliation: Laboratory of Cardiovascular Pharmacology, Faculty of Medical Sciences, University of Campinas, Campinas, SP, Brazil. Electronic address: hmoreno@uol.com.br.
authors.forename: Heitor
authors.initials: H
authors.lastname: Moreno
mesh_terms: D000959:Antihypertensive Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000097:blood; D004351:Drug Resistance; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D059289:Vascular Stiffness / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D015415:Biomarkers; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost
keywords: Arterial stiffness; Flow-mediated dilation; Oxidative stress; Refractory hypertension