Acute administration of L-arginine does not improve arterial endothelial function in chronic renal failure

Background. Reduced activity of the nitric oxide (NO) pathway has been impl icated in the endothelial dysfunction that occurs in patients with renal fa ilure. NO is generated from L-arginine by NO synthase, and certain uremic t oxins including asymmetrical dimethyl-L-arginine (ADMA), inhibit NO synthas e and might contribute to endothelial dysfunction. We hypothesized that exo genous L-arginine might improve endothelial function in patients with renal failure by overcoming the effects of uremic toxins. Methods. Endothelial function of the forearm resistance vasculature was ass essed using plethysmography to measure the dilator response to intra-arteri al acetylcholine (25 to 100 nmol/min). Endothelial function of radial and b rachial arteries was assessed using vascular ultrasound to measure the dila tor response to flow during reactive hyperemia (flow-mediated dilation; FMD ). Studies were performed before and after administration of L-arginine by intra-arterial infusion (50 mu mol/min) in 8 pre-dialysis patients or by in travenous infusion (10 g) in 18 hemodialysis patients. Results. Local L-arginine did not improve the dilator response of forearm r esistance vessels (AUC 23.1 +/- 6.4 pre, 23.1 +/- 5.1 post; P = 0.9) or FMD of the radial artery (6.5 +/- 1.2% pre. 6.3 +/- 0.8% post; P = 0.8). Syste mic L-arginine did not improve FMD of the brachial artery (4.1 +/- 1.1 % pr e, 3.0 +/- 1.1% post; P = 0.07). These data demonstrate that acute local or systemic administration of L-arginine did not improve endothelial function in resistance or conduit arteries of patients with chronic renal failure. Conclusion. The results suggest that competitive inhibition of nitric oxide synthase (NOS) by circulating inhibitors is not the principal explanation for impaired endothelial dilator function in chronic renal failure.