Year : 2011 | Volume
: 27 | Issue : 4 | Page : 566--567
Can serum asymmetric dimethylarginine become a marker of vasculogenic erectile dysfunction?
|How to cite this article:|
Kathpalia R. Can serum asymmetric dimethylarginine become a marker of vasculogenic erectile dysfunction?.Indian J Urol 2011;27:566-567
|How to cite this URL:|
Kathpalia R. Can serum asymmetric dimethylarginine become a marker of vasculogenic erectile dysfunction?. Indian J Urol [serial online] 2011 [cited 2020 Oct 25 ];27:566-567
Available from: https://www.indianjurol.com/text.asp?2011/27/4/566/91461
Penile erection is a dynamic vascular process that involves small vessels sensitive to functional and structural changes.  Damage to the endothelial lining of the arterial walls impairs the nitric oxide (NO) pathway and the ability for vasodilation. Endothelial dysfunction is an important pathophysiologic factor underlying both vasculogenic erectile dysfunction (ED) and atherosclerosis in other vascular beds. 
Recently, investigators have focused on the selective endogenous NO synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) as an important competitive inhibitor of NO formation.  Higher ADMA levels have been linked to traditional risk factors, preclinical atherosclerotic disease burden, and prediction of cardiovascular events.  However, the association of ADMA concentration with functional changes of the penile vascular bed has not been investigated till date.
Nikolaos et al. conducted a retrospective study enrolling 104 consecutive men with vasculogenic ED without any clinical evidence of coronary artery disease (CAD) from June 2005 to January 2007 and thirty one age-matched control subjects with normal erectile function. All patients were screened for socio-demographic data and cardio-vascular risk factors. The IIEF-5 questionnaire was used as the first step for evaluation of erectile performance in all participants (ED patients and controls). Doppler studies were performed only in ED patients by using 20 μg intracavernous prostaglandin E1 and audiovisual stimulation. Vasculogenic ED was diagnosed when the peak systolic velocity (PSV) was <35 cm/s and/or when the end diastolic velocity (EDV) was >5 cm/s. In both ED patients and controls, blood samples for measurement of ADMA were drawn at the first visit. On the basis of the median ADMA (0.64 mmol/l), population was divided into subjects with high and low ADMA concentration, and then further subdivided according to the presence or absence of arterial insufficiency.
Compared to men without ED, ED patients had significantly higher ADMA levels (0.65 ± 0.13 vs. 0.53 ± 0.11 mmol/l; P<0.001). In the whole ED group, ADMA levels were negatively associated with erectile performance as expressed by SHIM-5 score. ADMA levels of patients whose ED duration was >2 yr were significantly higher compared with the levels of subjects whose ED duration was <2 yr (0.69 ± 0.13 vs 0.60 ± 0.11 mmol/l; P=0.03). Univariate analysis revealed a significant inverse correlation between ADMA and PSV and a positive correlation between ADMA and EDV and levels of ADMA were significantly associated with progressively increasing severity of penile arterial disease (P <0.001).
Thus, it is the first study to demonstrate significantly high levels of ADMA among men with ultrasonographically documented vasculogenic ED and highlights the role of ADMA as a marker of penile arterial insufficiency implying its pathophysiologic contribution to processes associated with reduced arterial penile flow and generalized arterial disease associated with ED.
ADMA, a selective endogenous nitric oxide synthase inhibitor, is elevated in many conditions associated with ED including coronary artery disease (CAD). A common factor underlying both vasculogenic ED and atherosclerosis in other vascular beds is endothelial dysfunction. These two disorders are also linked at the clinical level: ED is common in patients with overt and silent coronary artery disease (CAD),  and it is increasingly being regarded as the early clinical manifestation of generalized vascular disease and carries an independent risk for future cardiovascular events. 
Little and conflicting information is available regarding the association of circulating ADMA levels with questionnaire-based ED severity and functional changes of the penile vascular bed. With an objective to determine the association of higher ADMA levels with extent of ultrasonographically documented penile vascular disease, authors showed an independent inverse association between ADMA level and peak systolic velocity (P<0.01) after adjusting for age, mean blood pressure, and other risk factors by multivariable analysis. ADMA was significantly increased in patients with severe arterial insufficiency (PSV <25 cm/s) compared to subjects with borderline insufficiency (PSV between 25 and 35 cm/s) and men with normal penile arterial function (P<0.001). 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.
To conclude, the study points out the role of ADMA as a marker of arterial damage in the penis and also provide mechanistic links for the association between ED and generalized arterial disease. Hence, an elevation of ADMA may call for more aggressive management of concomitant risk factors, because the combination of penile arterial insufficiency and higher circulating ADMA has been shown to be associated with a higher cardiovascular risk profile.
|1||Vardi Y, Dayan L, Apple B, Gruenwald I, Ofer Y, Jacob G. Penile and systemic endothelial function in men with and without erectile dysfunction. Eur Urol 2009;55:979-85.|
|2||Bivalacqua TJ, Liu T, Musicki B, Champion HC, Burnett AL. Endothelial nitric oxide synthase keeps erection regulatory function balance in the penis. Eur Urol 2007;51:1732-40.|
|3||Cooke JP. Asymmetrical dimethylarginine: The uber marker? Circulation 2004;109:1813-8.|
|4||Böger RH, Sullivan LM, Schwedhelm E, Wang TJ, Maas R, Benjamin EJ, et al. Plasma asymmetric dimethylarginine and incidence of cardiovascular disease and death in the community. Circulation 2009;119:1592-600.|
|5||Montorsi P, Ravagnani PM, Galli S, Salonia A, Briganti A, Werba JP, et al. Association between erectile dysfunction and coronary artery disease: Matching the right target with the right test in the right patient. Eur Urol 2006;50:721-31.|
|6||Thompson IM, Tangen CM, Goodman PJ, Probstfield JL, Moinpour CM, Coltman CA. Erectile dysfunction and subsequent cardiovascular disease. JAMA 2005;294:2996-3002.|