Asymmetric and symmetric dimethylarginine and sympathetic nerve traffic after renal denervation in patients with resistant hypertension

Guido Grassi, Gino Seravalle, Fosca Quarti Trevano, Domenico Spaziani, Filippo Scalise, Carla Auguadro, Patrizia Pizzini, Giovanni Tripepi, Graziella D’Arrigo, Francesca Mallamaci, Giuseppe Mancia, Carmine Zoccali

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background and objectives 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. Design, setting, participants, &measurements In this longitudinal study (follow-up: 2weeks–6months), repeated measurements over time ofmuscle 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 hypertensionwho 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 associatewith simultaneous changes in plasma levels of the two major endogenousmethylarginines,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.

Original languageEnglish
Pages (from-to)1560-1567
Number of pages8
JournalClinical Journal of the American Society of Nephrology
Volume10
Issue number9
DOIs
Publication statusPublished - Sep 4 2015

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Denervation
Hypertension
Kidney
Control Groups
Sympathetic Nervous System
N,N'-dimethylarginine
N,N-dimethylarginine
Nitric Oxide Synthase
Antihypertensive Agents
Longitudinal Studies
Heart Rate
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Nephrology
  • Transplantation
  • Epidemiology
  • Critical Care and Intensive Care Medicine

Cite this

Asymmetric and symmetric dimethylarginine and sympathetic nerve traffic after renal denervation in patients with resistant hypertension. / Grassi, Guido; Seravalle, Gino; Trevano, Fosca Quarti; Spaziani, Domenico; Scalise, Filippo; Auguadro, Carla; Pizzini, Patrizia; Tripepi, Giovanni; D’Arrigo, Graziella; Mallamaci, Francesca; Mancia, Giuseppe; Zoccali, Carmine.

In: Clinical Journal of the American Society of Nephrology, Vol. 10, No. 9, 04.09.2015, p. 1560-1567.

Research output: Contribution to journalArticle

Grassi, G, Seravalle, G, Trevano, FQ, Spaziani, D, Scalise, F, Auguadro, C, Pizzini, P, Tripepi, G, D’Arrigo, G, Mallamaci, F, Mancia, G & Zoccali, C 2015, 'Asymmetric and symmetric dimethylarginine and sympathetic nerve traffic after renal denervation in patients with resistant hypertension', Clinical Journal of the American Society of Nephrology, vol. 10, no. 9, pp. 1560-1567. https://doi.org/10.2215/CJN.01220215
Grassi, Guido ; Seravalle, Gino ; Trevano, Fosca Quarti ; Spaziani, Domenico ; Scalise, Filippo ; Auguadro, Carla ; Pizzini, Patrizia ; Tripepi, Giovanni ; D’Arrigo, Graziella ; Mallamaci, Francesca ; Mancia, Giuseppe ; Zoccali, Carmine. / Asymmetric and symmetric dimethylarginine and sympathetic nerve traffic after renal denervation in patients with resistant hypertension. In: Clinical Journal of the American Society of Nephrology. 2015 ; Vol. 10, No. 9. pp. 1560-1567.
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abstract = "Background and objectives 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. Design, setting, participants, &measurements In this longitudinal study (follow-up: 2weeks–6months), repeated measurements over time ofmuscle 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 hypertensionwho 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 associatewith simultaneous changes in plasma levels of the two major endogenousmethylarginines,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.",
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T1 - Asymmetric and symmetric dimethylarginine and sympathetic nerve traffic after renal denervation in patients with resistant hypertension

AU - Grassi, Guido

AU - Seravalle, Gino

AU - Trevano, Fosca Quarti

AU - Spaziani, Domenico

AU - Scalise, Filippo

AU - Auguadro, Carla

AU - Pizzini, Patrizia

AU - Tripepi, Giovanni

AU - D’Arrigo, Graziella

AU - Mallamaci, Francesca

AU - Mancia, Giuseppe

AU - Zoccali, Carmine

PY - 2015/9/4

Y1 - 2015/9/4

N2 - Background and objectives 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. Design, setting, participants, &measurements In this longitudinal study (follow-up: 2weeks–6months), repeated measurements over time ofmuscle 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 hypertensionwho 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 associatewith simultaneous changes in plasma levels of the two major endogenousmethylarginines,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.

AB - Background and objectives 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. Design, setting, participants, &measurements In this longitudinal study (follow-up: 2weeks–6months), repeated measurements over time ofmuscle 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 hypertensionwho 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 associatewith simultaneous changes in plasma levels of the two major endogenousmethylarginines,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.

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