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.

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.

• Authors: Lorenza Speranza, Sara Franceschelli, Nicolantonio D'Orazio, Raffaella Gaeta, Tonino Bucciarelli, Mario Felaco, Alfredo Grilli, Graziano Riccioni
• Journal: Microvascular research (Microvasc Res) Vol. 82 Issue 3 Pg. 391-6 (Nov 2011) ISSN: 1095-9319 [Electronic] United States
• PMID: 21722652 (Publication Type: Journal Article)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

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

Topics

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