RAPID ATRIAL PACING UPREGULATES SYNTHESIS OF ASYMMETRIC DIMETHYLARGININE IN CANINE AF MODEL

摘要

Plasma level of nitric oxide (NO) is shown to be decreased in atrial fibrillation (AF). Asymmetric dimethylarginine (ADMA) is an endogenous NO synthase inhibitor. We investigated the role of ADMA in suppression of NO. 10 HBD dogs were used. All dogs underwent radiofrequency catheter ablation of the AV node to create complete AV block and VVI pacemaker implantation to control ventricular rate at 100 bpm. Atrial pacemaker was also implanted. The dogs were divided into 2 groups, sham and AF group. In sham group, VVI pacing was performed without atrial pacing. In AF group, rapid atrial pacing at 540 bpm was performed for 10 weeks. ADMA was measured by HPLC. Plasma ADMA level was higher in AF group (3.12+-0.90 versus 0.30+-0.13 umol/L, P<0.01). Gene expression of protein arginine N-methyltransferases (PRMT1, ADMA synthase) in the atrium was enhanced by 1.4 fold in AF group (P<0.05). The activity, but not the gene expression of dimethylarginine dimethylaminohydrolase (DDAH, degrade ADMA), was reduced in AF group (P<0.05). Plasma NOx level was reduced in AF group (15.3+-2.1 versus 7.4+-2.9 umol/L, P<0.05). These results indicate that rapid atrial pacing induced upregulation of PRMT1 and reduction of DDAH activity causes ADMA accumulation and reduction of NO.