The biological effect of pharmacological treatment on dimethylaminohydrolases (DDAH-1) and cationic amino acid transporter-1 (CAT-1) expression in patients with acute congestive heart failure

Microvasc Res. 2011 Nov;82(3):391-6. doi: 10.1016/j.mvr.2011.06.003. Epub 2011 Jun 23.

Abstract

Aim: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) which plays an important role in controlling vascular tone and regulates the contractile properties of cardiac myocytes. The aim of this study was to investigate the effect of pharmacological treatment on symmetric dimethylarginine (SDMA), ADMA and arginine plasma concentrations in patients with acute congestive heart failure (ACHF) through the evaluation of type-1 system cationic amino acid transporter-1/type 1 dimethylarginine dimethylaminohydrolases-1 (CAT-1/DDAH-1).

Methods and results: 25 hospitalized cardiology patients with symptomatic acute congestive HF (NYHA Class III-IV) and impaired left ventricular (LV) function (ejection fraction<35%) were included in the study. ADMA, SDMA, and arginine plasma concentrations were assessed before and after pharmacological treatment by high performance liquid chromatography. All patients received an adequate pharmacological treatment for ACHF. ADMA and SDMA plasma levels were significantly higher after pharmacological treatment respect to baseline values (pre-treatment) (0.75 vs 0.48; 1.31 vs 1.03; p<0.01). Arginine plasma concentration was significantly lower after therapy respect to baseline values (0.78 vs 0.99; p<0.01). This is associated more with the modulation of DDAH-1 protein than with of CAT-1 system transport.

Conclusions: In patients with ACHF, acute renal impairment function and the modulation of metabolism and extracellular transport by the DDAH-1/CAT-1 system determine high ADMA and SDMA levels after therapy for acute congestive heart failure.

MeSH terms

  • Acute Disease
  • Aged
  • Amidohydrolases / metabolism*
  • Arginine / analogs & derivatives
  • Arginine / blood
  • Cardiovascular Agents / therapeutic use*
  • Cationic Amino Acid Transporter 1 / drug effects*
  • Cationic Amino Acid Transporter 1 / metabolism
  • Chromatography, High Pressure Liquid
  • Echocardiography, Doppler
  • Female
  • Heart Failure / blood
  • Heart Failure / drug therapy*
  • Heart Failure / enzymology
  • Heart Failure / physiopathology
  • Humans
  • Italy
  • Male
  • Middle Aged
  • Stroke Volume / drug effects
  • Treatment Outcome
  • Ventricular Function, Left / drug effects

Substances

  • Cardiovascular Agents
  • Cationic Amino Acid Transporter 1
  • SLC7A1 protein, human
  • symmetric dimethylarginine
  • N,N-dimethylarginine
  • Arginine
  • Amidohydrolases
  • dimethylargininase