title: Asymmetric and Symmetric Dimethylarginine and Sympathetic Nerve Traffic after Renal Denervation in Patients with Resistant Hypertension.
abstract: OBJECTIVE
  The plasma concentration of the endogenous inhibitor of nitric oxide synthase asymmetric dimethylarginine (ADMA) associates with sympathetic activity in patients with CKD, but the driver of this association is unknown.
  
  
  METHODS
  In this longitudinal study (follow-up: 2 weeks-6 months), repeated measurements over time of muscle sympathetic nerve activity corrected (MSNAC), plasma levels of ADMA and symmetric dimethylarginine (SDMA), and BP and heart rate were performed in 14 patients with drug-resistant hypertension who underwent bilateral renal denervation (enrolled in 2013 and followed-up until February 2014). Stability of ADMA, SDMA, BP, and MSNAC over time (6 months) was assessed in two historical control groups of patients maintained on stable antihypertensive treatment.
  
  
  RESULTS
  Time-integrated changes in MSNAC after renal denervation ranged from -40.6% to 10% (average, -15.1%), and these changes were strongly associated with the corresponding changes in plasma ADMA (r= 0.62, P=0.02) and SDMA (r=0.72, P=0.004). Changes in MSNAC went along with simultaneous changes in standardized systolic (r=0.65, P=0.01) and diastolic BP (r=0.61, P=0.02). In the historical control groups, no change in ADMA, SDMA, BP, and MSNAC levels was recorded during a 6-month follow-up.
  
  
  CONCLUSIONS
  In patients with resistant hypertension, changes in sympathetic activity after renal denervation associate with simultaneous changes in plasma levels of the two major endogenous methylarginines, ADMA and SDMA. These observations are compatible with the hypothesis that the sympathetic nervous system exerts an important role in modulating circulating levels of ADMA and SDMA in this condition.
authors.affiliation: Clinica Medica, Dipartimento di Scienze della Salute, Università Milano-Bicocca, Milan, Italy; IRCCS Multimedica, Sesto San Giovanni, Milan, Italy;
authors.forename: Guido
authors.initials: G
authors.lastname: Grassi
authors.affiliation: Istituto Auxologico Italiano, Milan, Italy;
authors.forename: Gino
authors.initials: G
authors.lastname: Seravalle
authors.affiliation: Clinica Medica, Dipartimento di Scienze della Salute, Università Milano-Bicocca, Milan, Italy;
authors.forename: Fosca Quarti
authors.initials: FQ
authors.lastname: Trevano
authors.affiliation: Unità Operativa di Cardiologia, Ospedale Magenta, Milan, Italy;
authors.forename: Domenico
authors.initials: D
authors.lastname: Spaziani
authors.affiliation: Cardiologia Interventistica, Policlinico di Monza, Monza, Italy; and.
authors.forename: Filippo
authors.initials: F
authors.lastname: Scalise
authors.affiliation: Cardiologia Interventistica, Policlinico di Monza, Monza, Italy; and.
authors.forename: Carla
authors.initials: C
authors.lastname: Auguadro
authors.affiliation: CNR-IFC, Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, Reggio Calabria, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Pizzini
authors.affiliation: CNR-IFC, Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, Reggio Calabria, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tripepi
authors.affiliation: CNR-IFC, Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, Reggio Calabria, Italy.
authors.forename: Graziella
authors.initials: G
authors.lastname: D'Arrigo
authors.affiliation: CNR-IFC, Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, Reggio Calabria, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Mallamaci
authors.affiliation: Istituto Auxologico Italiano, Milan, Italy;
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mancia
authors.affiliation: CNR-IFC, Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, Reggio Calabria, Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: Zoccali
mesh_terms: D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D001794:Blood Pressure; D004351:Drug Resistance; D005260:Female; D006339:Heart Rate; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology / Q000601:surgery*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000294:innervation; D013562:Sympathectomy; D013564:Sympathetic Nervous System / Q000503:physiopathology*
chemical_list: C024917:symmetric dimethylarginine; C018524:N,N-dimethylarginine; D001120:Arginine
keywords: ADMA; CKD; hypertension; renal denervation