Transpulmonary vascular gradients of nitric oxide pathway metabolites and asymmetrical dimethyl-L-arginine in the flow – or pressure-overloaded pulmonary vasculature

Transpulmonary gradients of nitrite (NO2), nitrate (NO3) and ADMA were determined in patients with increased pulmonary flow (Qp) before (1) and after (2) interventional closure of atrial septal defect (ASD), and in patients with increased pulmonary vascular resistance (Rp) (3). Twenty patients with ASD: median age 6.1 years (range 3.5–17.1 years), median Qp/Qs 2.1, Rp/Rs < 0.12. Twenty patients with PH: median age 8.1 years (range 1.2–13.5 years), median Rp/Rs 1.1 (range 0.36–1.79). NO2, NO3 (chromatography mass spectrometry) and ADMA (high-performance liquid chromatography) were measured in plasma samples from the main pulmonary artery (PA) and femoral artery (SA).(1) In ASD patients, NO2 showed a significant gradient with a median SA : PA ratio of 1.34 (P < 0.01), but this was not so for ADMA (1.05) or NO3 (1.01). (2) After closure, SA : PA ratio of NO2 decreased to 0.89 (P < 0.05), indicating a switch from NO2 production to NO2 consumption, whereas ADMA (1.00) and NO3 (0.99) remained unchanged. (3) In PH, significant transpulmonary gradients were observed for ADMA (1.11; P < 0.05) and NO3 (1.03), but not for NO2 (0.84). Median levels of ADMA in SA (4.08 μmol/l) were higher than those in ASD before (3.67 μmol/l) and after (3.55 μmol/l) closure (P < 0.05).Analysis of transpulmonary metabolite gradients may provide significant insights into the vascular NO pathway in the overloaded pulmonary circulation. Reversible augmentation of intra-pulmonary vascular NO synthesis in ASD patients contrasts with the inappropriate NO synthesis in patients with increased Rp, to which intrapulmonary ADMA formation may significantly contribute.