title: Nebivolol treatment reduces serum levels of asymmetric dimethylarginine and improves endothelial dysfunction in essential hypertensive patients.
abstract: BACKGROUND
  This study was conducted to evaluate (i) the effect of nebivolol, a selective beta1-adrenergic receptor antagonist, on plasma concentration of asymmetric dimethylarginine (ADMA) and on flow-mediated dilation (FMD) in essential hypertensive patients; (ii) the effect of serum derived from the treated hypertensive patients on ADMA and on dimethylarginine dimethylaminohydrolase 2 (DDAH2), the enzyme that selectively degrades ADMA, in human umbilical vein endothelial cells (HUVECs).
  
  
  METHODS
  Forty healthy subjects and 40 matched essential hypertensive patients treated with atenolol and nebivolol according to a double-blind, randomized design participated in the study. Evaluation of brachial artery (BA) reactivity was performed by a longitudinal B-mode scan of the right BA. ADMA and L-arginine were measured by high-performance liquid chromatography. DDAH2 expression and endothelial nitric oxide synthase activity (eNOS) were also evaluated in HUVECs.
  
  
  RESULTS
  ADMA levels were significantly decreased and FMD increased only in patients receiving nebivolol (P < 0.01). Furthermore, in nebivolol group, we found a significant correlation between changes in ADMA levels and changes in FMD (P < 0.01). Sera derived from patients treated with nebivolol but not with atenolol decreased ADMA and increased DDAH2 expression and eNOS activity (P < 0.001) in HUVECs.
  
  
  CONCLUSIONS
  The results of this study demonstrate that the improvement of endothelial dysfunction induced by nebivolol in hypertensive patients may be related to its effect on circulating ADMA levels. Although the mechanism by which nebivolol reduces circulating ADMA in hypertensive patients remains unclear, our ex vivo results suggest that the upregulation of DDAH2 expression may have a role.
authors.affiliation: Department of Biomedical and Surgical Sciences, Section of Internal Medicine, University of Verona, Italy.
authors.forename: Anna Fratta
authors.initials: AF
authors.lastname: Pasini
authors.forename: Ulisse
authors.initials: U
authors.lastname: Garbin
authors.forename: Chiara
authors.initials: C
authors.lastname: Stranieri
authors.forename: Veronica
authors.initials: V
authors.lastname: Boccioletti
authors.forename: Chiara
authors.initials: C
authors.lastname: Mozzini
authors.forename: Stefania
authors.initials: S
authors.lastname: Manfro
authors.forename: Andrea
authors.initials: A
authors.lastname: Pasini
authors.forename: Mattia
authors.initials: M
authors.lastname: Cominacini
authors.forename: Luciano
authors.initials: L
authors.lastname: Cominacini
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000368:Aged; D000581:Amidohydrolases / Q000378:metabolism; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D001262:Atenolol / Q000494:pharmacology / Q000627:therapeutic use; D001578:Benzopyrans / Q000494:pharmacology* / Q000627:therapeutic use; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D004983:Ethanolamines / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D000068577:Nebivolol; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D001578:Benzopyrans; D004983:Ethanolamines; D000068577:Nebivolol; D001262:Atenolol; C018524:N,N-dimethylarginine; D001120:Arginine; D052250:Nitric Oxide Synthase Type III; D000581:Amidohydrolases; C059999:dimethylargininase