The effect of plasma asymmetric dimethylarginine (ADMA) level and L-arginine/ADMA ratio on the development of coronary collaterals

Objectives: It has been shown that asymmetric dimethylarginine (ADMA), an endogenous competitive antagonist of nitric oxide (NO) synthase, inhibits angiogenesis by reducing the production and bioavailability of NO. We investigated the effect of plasma ADMA level and L-arginine/ADMA ratio on the development of coronary collateral arteries. Study design: The study consisted of 94 patients (66 males, 28 females; mean age 59 +/- 11 years) who underwent coronary angiography for suspected coronary artery disease and were found to have severe stenosis (> 95%) in at least one major coronary artery. The patients were evaluated in two groups with poor ( Rentrop score 0-1, n= 44) and good (score 2-3, n= 50) coronary collateral circulation according to the Rentrop collateral scoring system. Plasma levels of ADMA and L-arginine were measured by high-performance liquid chromatography. Results: The two groups were similar with regard to basal characteristics and cardiovascular risk factors (p> 0.05) except for stable angina, which was more common in patients with Rentrop score 2-3 collateral circulation (p< 0.001). Despite similar L- arginine levels ( p> 0.05), patients with Rentrop score 0-1 had a significantly higher ADMA level (p= 0.003) and lower L-arginine/ADMA ratio (p= 0.019). Multivariate logistic regression analysis showed that plasma ADMA concentration was an independent predictor of coronary collateral development (odds ratio=0.674; 95% confidence interval= 0.508-0.894; p= 0.006). Conclusion: Elevated plasma ADMA concentrations are associated with a poorly developed coronary collateral circulation, suggesting that dysregulation of the NO synthase pathway may result in impaired collateral development.