Letters to the Editor
Do Homoarginine and Asymmetric Dimethylarginine Act Antagonistically in the Cardiovascular System?
2014 Volume 78 Issue 8 Pages 2094-2095
Details
2014 Volume 78 Issue 8 Pages 2094-2095
To the Editor:
We read with great interest the article by Sobczak et al.1 Interestingly, the authors observed that, on average, smoking healthy men had lower homoarginine (hArg) plasma concentrations than nonsmoking healthy men (1.53 vs. 1.98 µmol/L), while the plasma concentrations of asymmetric dimethylarginine (ADMA) were slightly higher in the smokers (0.36 vs. 0.35 µmol/L). We wish to comment on this study.
It is well established that high circulating concentrations of ADMA are a cardiovascular risk factor. Only very recently, low circulating concentrations of hArg have been proposed as a cardiovascular risk factor too.2 The underlying mechanisms of ADMA’s and hArg’s actions in the cardiovascular system are not fully understood. Generally, ADMA and hArg are believed to be involved in the L-arginine/nitric oxide (NO) pathway, namely ADMA as an inhibitor and hArg as a substrate of NO synthesis. One may therefore assume that ADMA and hArg are antagonists in this scenario. Under the restriction of the lack of knowledge of the exact mechanisms of action and potency of ADMA and hArg as cardiovascular risk factors, we think that the extent of the molar ratio of circulating ADMA and hArg (ie, hArg/ADMA) and its direction of change may provide more useful information than their absolute concentrations in the blood (Table, Figure). In a previous study, we found that the median hArg/ADMA ratio was lower in early preeclampsia compared with unaffected pregnant women (7 vs. 9).5 Based on the data reported by Valtonen et al,3 the mean hArg/ADMA ratio in normal pregnancy increases with gestation in approximation from 6 to 10, while the mean hArg/ADMA ratio in nonpregnant women is calculated to be approximately 5. The mean hArg/ADMA ratio calculated from the data reported by Sobczak et al1 was smaller in smokers compared with nonsmokers (≈4.2 vs. 5.7).
| Reference | hArg/ADMA ratio | Health, disease, condition |
|---|---|---|
| Valtonen et al3 | 5 | Healthy nonpregnant women |
| 6–10 | Normal pregnancy | |
| März et al2 | 1.3 | Hemodialysis patients |
| 3.3 | Cardiac-risk patients | |
| Pilz et al4 | 1.7, 2.7, 3.4, 4.8 | Heart disease |
| Khalil et al5 | 7 | Early preeclampsia |
| 9 | Normal pregnancy | |
| Sobczak et al1 | 4.2 | Healthy smokers (male) |
| 5.7 | Healthy nonsmokers (male) | |
| Tomaschitz et al6 | 1.9, 2.9, 4.4 | Cardiovascular diseases |
| van der Zwan et al7 | 3.3 | Elderly men and women (Hoorn study) |
| Pilz et al8 | 2.0, 2.8, 3.3, 4.4 | Elderly men and women (Hoorn study) |
| Kayacelebi et al9 | 3.4 | Takotsubo cardiomyopathy (n=23) |
| 4.7 (P=0.0036) | Healthy women (n=9) |
ADMA, Asymmetric Dimethylarginine; hArg, Homoarginine.
Molar ratio of homoarginine to asymmetric dimethylarginine (hArg/ADMA) in plasma of 23 patients suffering from takotsubo cardiomyopathy (Takotsubo) and of 9 healthy subjects (Control). The hArg/ADMA ratio was calculated by using the plasma hArg concentrations measured in a previous study.9 ADMA concentrations were newly measured in the same samples by GC-MS/MS.10
In healthy humans, hArg is present in plasma and serum at concentrations approximately 5-fold those of ADMA. The concentration of circulating hArg varies far more widely than the concentration of circulating ADMA, suggesting that the synthesis, metabolism and elimination of ADMA are more closely controlled than those of hArg. As the extent of the hArg/ADMA ratio is mainly determined by the concentration of circulating hArg, the hArg/ADMA ratio may be a more dependable parameter of the importance and interplay of hArg and ADMA in the circulation than the examination of single biomarkers. Reference values and intervals for the hArg/ADMA ratio remain to be established by accurately measuring blood concentrations of hArg and ADMA. Cardiovascular diseases, aging and smoking seem to be associated with smaller, and pregnancy with higher, hArg/ADMA ratios. Increasing the hArg/ADMA ratio in blood by nutrition and/or pharmacological treatment may represent a novel means of improving and possibly preventing cardiovascular diseases.
Conflict of Interest: none.
(Released online June 16, 2014)
