Evaluation of asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) in patient with erectile dysfunction (ED)

Introduction. Erectile dysfunction (ED) has been defined as the inability to achieve and/or to maintain penile erection of sufficient quality to allow a satisfactory sexual intercourse. It has been suggested that endothelial dysfunction is linked to ED as they share a dependence on a common pathway through the release of nitric oxide (NO). Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) are derived from post-translational methylation of arginine residues. ADMA is a competitive inhibitor of NO synthase (NOS) and modification of ADMA concentrations has been shown to change vascular NO production and thereby vascular tone and systemic vascular resistance. SDMA does not directly inhibit the NOS but is able to interfere with NO synthesis. The aim of the present study was to investigate the concentrations of ADMA and SDMA in patients with arteriogenic and non arteriogenic ED. Patients and Methods. 29 patients and 30 healthy controls, matched for age, were included in this study. The 29 patients [mean age 44y, range 19-63] underwent eco colour Doppler assessment of cavernosal arteries in conjunction with intracavernous injection (ICI) of prostaglandin E1 to induce an erection. In accordance with Helsinki Declaration II, the design and execution of the experiment were explained thoroughly to the participants, and informed consent was obtained. The Doppler parameter of peak systolic velocity (PSV) was recorded 5, 10, and 20 min after ICI. Arteriogenic ED was diagnosed when the PSV was less than 35 cm/s. ADMA and SDMA were assayed by HPLC (1). Plasma (0.1mL) was added with L-homoarginine as internal standard and applied to a pre-activated cation-exchange SPE cartridge (Phenomenex STRATA SCX) on a vacuum system. After washings with TCA 2%, phosphate buffer pH 8.0 and methanol, the amino acids were eluted with 1mL of a methanol:water solution (70:30, v:v) containing 2% triethylamine. The eluate was dried under nitrogen, dissolved in 0.1mL bi-distilled water, derivatized with the OPA reagent and injected into an HPLC equipped with a fluorescent detector (λecc 340 nm, λem 455 nm) and with an Ultrasphere ODS column (250x4.6mm, 5μm) protected by a guard-column LiChrospher RP-18. The gradient analysis was performed at room temperature, at a flow-rate of 1.1mL/min with a mobile phase consisting of A (sodium citrate buffer, 50mmol/L, pH 6.2) and B (distilled water: acetonitrile:methanol; 1:2:2; v:v:v). The total run time, including the column washing, was 32 min. Results. The mean ADMA and SDMA levels (mean±SD) were significantly higher in patients with ED [0.56±0.13 μmol/L (p=0.003) and 0.68±0.16 μmol/L (p=0.001), respectively] than in healthy controls [0.47±0.12 μmol/L and 0.46±0.08 μmol/L, respectively]. Between patients with arteriogenic [n=15, mean age 47y, range 28-63] [0.55±0.12 μmol/L and 0.65±0.12 μmol/L, respectively] and non arteriogenic ED [n=14, mean age 41y, range 19-62] [0.56±0.13 μmol/L and 0.67±0.18 μmol/L, respectively] a statistical significant associations (p>0.05) were not found. Discussion and conclusion. Our preliminary data show increased levels of ADMA and SDMA in patients with ED compared to healthy subjects, however ADMA and SDMA concentrations do not appear correlated with PSV. References. Paroni R, et al. Amino Acids 2005;28:389-394.