title: Macrophage Superoxide Anion Production in Essential Hypertension: Associations With Biological and Psychological Cardiovascular Risk Factors.
abstract: Essential hypertension is an important risk factor for coronary artery disease and its underlying process atherosclerosis, but involved mechanisms are not fully understood. Both macrophages and superoxide anions have been proposed to play a major role in the pathogenesis of atherosclerosis. In the present study, we investigated whether macrophages of individuals with hypertension show higher nicotinamide adenine dinucleotide phosphate oxidase-derived superoxide anion production compared with normotensive individuals. Furthermore, we examined associations between macrophage superoxide anion production and the psychological factors depression and chronic stress independent from hypertension status.
  
  
  
  We studied 30 hypertensive (mean [standard deviation] = 48.7 [2.4] years) and 30 age-matched normotensive men (mean [standard deviation] = 48.6 [2.4] years). We assessed macrophage superoxide anion production using the WST-1 assay. The assay is based on the chemical reduction of the cell-impermeative tetrazolium salt WST-1 by superoxide anions that are produced by activated human ex vivo isolated monocyte-derived macrophages. We further evaluated whether chronic stress or depressive symptom severity was associated with macrophage superoxide anion production. All analyses were adjusted for potential confounders.
  
  
  
  Individuals with hypertension showed higher superoxide anion production compared with normotensive individuals (F(1,58) = 11.56, p = .001). Complementary analyses using mean arterial blood pressure as a continuous measure revealed that higher mean arterial pressure correlated significantly with higher WST-1 reduction (ß = .38, p = .003, ΔR = .145). These results remained significant when controlling for potential confounding influences. Chronic stress was related to higher WST-1 reduction scores, but this association was not statistically significant (ß = .24, p = .067, ΔR = .053); depression levels were not significantly associated with WST-1 reduction scores (p = .24).
  
  
  
  Our results indicate higher macrophage superoxide anion production in individuals with hypertension compared with normotensive individuals. This may suggest a mechanism underlying cardiovascular risk with hypertension.
authors.affiliation: Biological and Health Psychology (Zuccarella-Hackl, Thomas, Wirtz), Department of Clinical Research (Zuccarella-Hackl, von Känel, Widmer), University of Bern, Bern, Switzerland; Department of Neurology (von Känel), Biological Work and Health Psychology, University of Konstanz, Konstanz, Germany (Hauser), Inselspital, Bern University Hospital, Bern, Switzerland; Clinical Psychology and Psychotherapy (Kuebler), University of Zurich, Zurich, Switzerland; Department of Psychosomatic Medicine (von Känel), Clinic Barmelweid, Barmelweid, Switzerland; Biological Work and Health Psychology (Wirtz, Thomas), University of Konstanz, Konstanz, Germany; and Department of Neurosurgery (Widmer), Inselspital, Bern University Hospital, Bern, Switzerland.
authors.forename: Claudia
authors.initials: C
authors.lastname: Zuccarella-Hackl
authors.forename: Roland
authors.initials: R
authors.lastname: von Känel
authors.forename: Livia
authors.initials: L
authors.lastname: Thomas
authors.forename: Mark
authors.initials: M
authors.lastname: Hauser
authors.forename: Ulrike
authors.initials: U
authors.lastname: Kuebler
authors.forename: Hans Rudolf
authors.initials: HR
authors.lastname: Widmer
authors.forename: Petra H
authors.initials: PH
authors.lastname: Wirtz
mesh_terms: D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000378:metabolism*; D000075222:Essential Hypertension; D005260:Female; D006801:Humans; D006973:Hypertension / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019255:NADPH Oxidases / Q000378:metabolism*; D012307:Risk Factors; D013481:Superoxides / Q000378:metabolism*; D055815:Young Adult
chemical_list: D013481:Superoxides; D019255:NADPH Oxidases