O-20135 Rapid atrial pacing upregulates synthesis of asymmetrical dimethylarginine and expression of protein arginine N-methyltransferases in canine AF model

Plasma level of nitric oxide (NO) is shown to be decreased in atrial fibrillation (AF). Asymmetrical dimethylarginine (ADMA) is an endogenous NO synthase inhibitor. We investigated the role of ADMA in suppression of NO. In 14 HBD dogs, atrioventricular block was created (ventricular pacing 100 bpm). Atrial pacing (540 bpm) was done for 6 weeks, and additional pacing for 4 weeks was done with (AF+AMD group, n=5) or without (AF group, n=5) oral AMD (30mg/kg/day). In the other 4 dogs, atrial pacing was not done (sham group, n=4). ADMA was measured by HPLC. Plasma level of ADMA was significantly higher in AF group (3. 12±0. 90 μmol/L) than in sham group (0. 30±0. 13 μmol/L, P=0. 0008). Gene expression of protein arginine N-methyltransferases (PRMT1, ADMA synthase) in the atrium, which was assessed by PT-PCR, was enhanced by 1. 4-fold in AF group compared with that in sham group (P=0. 0147). Neither ADMA level nor PRMT1 expression was affected with AMD. Plasma level of ADMA is elevated in this AF model being associated with upregulation of PRMT1.