Relationship of asymmetric dimethylarginine with penile Doppler ultrasound parameters in men with vasculogenic erectile dysfunction

Abstract

Background: Asymmetric dimethylarginine (ADMA), a selective endogenous nitric oxide synthase inhibitor, is elevated in many conditions associated with erectile dysfunction (ED), such as hypertension, diabetes, hyperlipidemia, and renal failure; it is also increased in men with coronary artery disease and ED. The dynamic penile colour Doppler ultrasound is considered the gold standard for the evaluation of penile vascular damage.

Objective: We investigated whether the extent of ultrasonographically documented penile vascular disease is associated with higher ADMA levels.

Design, setting, and participants: One hundred four consecutive ED patients (mean age: 56 ± 9 yr) without manifest cardiovascular/atherosclerotic disease and 31 subjects with normal erectile function matched for age and traditional risk factors were studied.

Measurements: We evaluated penile dynamic colour Doppler parameters of arterial insufficiency (peak systolic velocity) and veno-occlusive dysfunction (end diastolic velocity) and measured systemic inflammatory markers/mediators.

Results and limitations: Compared to men without ED, ED patients had significantly higher ADMA levels (p<0.001). ADMA was significantly increased in patients with severe arterial insufficiency (PSV<25 cm/s) compared to subjects with borderline insufficiency and men with normal penile arterial function (p<0.001, by analysis of variance). Multivariable analysis adjusting for age, mean pressure, other risk factors, high-sensitivity C-reactive protein, testosterone, and treatment showed independent inverse association between ADMA level and peak systolic velocity (p<0.01). The combination of higher ADMA level with arterial insufficiency showed greater impact on 10-yr risk of a cardiovascular event compared to either parameter alone.

Conclusions: ADMA level is independently associated with ultrasonographically documented poor penile arterial inflow. This finding underlines the important role of ADMA as a marker of penile arterial damage and implies a contribution of this compound to the pathophysiology of generalised vascular disease associated with ED.