Increased plasma asymmetric dimethylarginine (ADMA) in rats with 5/6 nephrectomy (NX) is associated with increased synthesis by protein arginine methyltransferase (PRMT) and decreased breakdown by dimethylarginine dimethylaminohydrolase (DDAH)

Background: Plasma ADMA and oxidative stress are elevated in chronic kidney disease (CKD). We previously reported that 5/6 NX rats developed significant glomerulosclerosis which was attenuated by the antioxidant vitamin E (Vit E). The 5/6 NX group increased renal cortex NADPH‐dependent superoxide production vs. sham which was completely prevented by Vit E. Here we investigate the impact of 5/6 NX (by surgical excision of kidney tissue) on plasma ADMA and renal expression of PRMT1 and DDAH, as well as DDAH activity. We also investigated the impact of Vit E on ADMA and DDAH in 5/6 NX. Materials and Methods: We studied 3 groups of male SD rats: sham (n=6), 5/6 NX (n=6), and 5/6 NX treated with Vit E (2000 U/kg food) (n=5). Rats were sacrificed 15 wk after surgery. Results: Both 5/6 NX groups showed similar increases in plasma ADMA levels vs. sham. Renal cortex DDAH1 and DDAH2 protein expression was not different between 3 groups. However, the in vitro renal DDAH activity was decreased in 5/6 NX rats and this was not prevented by Vit E. Renal cortex PRMT1 expression was increased in 5/6 NX rats. Conclusions: ADMA levels rise in 5/6NX in association with increased PRMT protein and decreased DDAH activity in kidney. This reinforces the notion that kidney plays a significant role in regulation of ADMA levels. Unexpectedly, the antioxidant action of Vit E did not prevent the increase in ADMA and decrease in DDAH activity.