title: Nitric oxide dysregulation in patients with heart failure: the association of depressive symptoms with L-arginine, asymmetric dimethylarginine, symmetric dimethylarginine, and isoprostane.
abstract: OBJECTIVE
  Nitric oxide (NO) regulation plays a critical role in cardiovascular diseases including heart failure (HF). Markers of NO dysregulation have been found in individuals with depression without cardiovascular disease. Because depression is associated with poor HF outcomes, the present study tested the hypothesis that depression is associated with a dysregulated NO pathway in patients with HF.
  
  
  METHODS
  Serum levels of NO regulation (L-arginine, asymmetric dimethylarginine [ADMA], and symmetric dimethylarginine [SDMA]) and oxidative stress (isoprostane 8-epi prostaglandin F2α) were measured in 104 patients with HF (mean [standard deviation] age = 65.7 [8.4] years, 28% women) at baseline and 12 months. Depressive symptoms were measured using the Beck Depression Inventory. The associations between depressive symptoms with markers of NO regulation were examined with mixed-model analysis, adjusted for age, sex, time of assessment, left ventricular ejection fraction, creatinine, and hypertension.
  
  
  RESULTS
  Depressive symptoms were correlated with a lower L-arginine/ADMA ratio (r = -0.22, p = .003) and higher SDMA levels (r = 0.28, p < .001). Associations were similar for somatic depressive symptoms and cognitive-affective symptoms (L-arginine/ADMA ratio: r = -0.20 [p = .009] versus r = -0.19 [p = .013]; ADMA: r = 0.16 [p = .043] versus r = 0.10 [p = .20]; SDMA: r = 0.27 [p < .001] versus r = 0.22 [p = .005], respectively). No associations were found between depressive symptoms and isoprostane. The association between depression and the L-arginine/ADMA ratio remained significant in multivariate adjusted models.
  
  
  CONCLUSIONS
  Depressive symptoms were associated with markers of NO dysregulation, particularly the L-arginine/ADMA ratio and SDMA, in patients with HF. The lower L-arginine/ADMA ratio indicates less available NO, suggesting that NO-related endothelial dysfunction may play a role in the adverse risk of HF progression associated with depression.
authors: From the Department of Medical and Clinical Psychology (Mommersteeg, Kop), CoRPS, Center of Research on Psychology in Somatic Diseases, Tilburg University, Tilburg, the Netherlands; Department of Molecular Neurobiology (Schoemaker, Eisel), University of Groningen, Groningen, the Netherlands; Departments of Cardiology (Schoemaker) and Neurology and Alzheimer Research Centre (Eisel), University Medical Centre Groningen, Groningen, the Netherlands; Department of Internal Medicine (Garrelds), Division of Vascular Medicine and Pharmacology, Erasmus Medical Center, the Netherlands; and Department of Internal Medicine (Schalkwijk), Laboratory for Metabolism and Vascular Medicine, CARIM, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors: Paula M C
authors: PM
authors: Mommersteeg
authors: Regien G
authors: RG
authors: Schoemaker
authors: Ulrich L M
authors: UL
authors: Eisel
authors: Ingrid M
authors: IM
authors: Garrelds
authors: Casper G
authors: CG
authors: Schalkwijk
authors: Willem J
authors: WJ
authors: Kop
mesh_terms: D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood; D003863:Depression / Q000097:blood* / Q000150:complications / Q000378:metabolism; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000150:complications / Q000378:metabolism; D006801:Humans; D028421:Isoprostanes / Q000097:blood; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D018384:Oxidative Stress
chemical_list: D028421:Isoprostanes; D009569:Nitric Oxide; C024917:symmetric dimethylarginine; C018524:N,N-dimethylarginine; D001120:Arginine