Asymmetrical dimethylarginine in systemic sclerosis-related pulmonary arterial hypertension

Objectives. SSc is a CTD characterized by vascular involvement, with generalized disturbance of the microcirculation, which may lead to pulmonary artery hypertension (PAH). Asymmetrical dimethylarginine (ADMA) is an endogenous nitric oxide (NO) inhibitor. Increased concentrations of plasma ADMA may also contribute to endothelial dysfunction in patients with pulmonary vascular disease. The aim of our study was to elucidate the possible relationship between serum ADMA and PAH in patients with SSc. Moreover, we sought to investigate the effect of ADMA levels on the functional capacity of these patients. Methods. Plasma ADMA levels were measured in 66 patients with SSc (63 females, mean age 57.8 +/- 12.8 yrs, median duration of disease 9.9 yrs, 47 with lcSSc and 19 with dcSSc disease) and 30 healthy controls (29 females, mean age 58.2 +/- 8.4 yrs). Systolic pulmonary artery pressure (sPAP) assessed by echocardiography, lung function tests, 6-min walk test (6MWT) and serum ADMA levels were recorded from patients. Results. In 24 patients, the diagnosis of PAH was established. Mean value of ADMA for SScPAH patients was 0.44 +/- 0.22 mu mol/l compared with 0.26 +/- 0.18 mu mol/l for patients without PAH and 0.25 +/- 0.20 mu mol/l for controls (P = 0.001). ADMA levels were inversely correlated with the 6MWT (r = -0.55, P = 0.005). Conclusions. In patients with SScPAH, increased ADMA serum levels and their negative association with exercise capacity suggests that the NO pathway is involved in the development of pulmonary vascular disease.