Previous work demonstrated that L-arginine, the substrate for nitric oxide synthase, is carried into inner medullary collecting duct (IMCD) cells via system y+, that the major system y+ gene product in IMCD is the cationic amino acid transporter 1 (CAT1), and that blockade of L-arginine uptake in the renal medulla decreases NO and leads to systemic hypertension. The present study determined the influence of dietary sodium intake on L-arginine uptake in IMCD, on CAT1 immunoreactive protein in the renal medulla, and on the hypertensive response to blockade of L-arginine uptake in the renal medulla. Transport studies in bulk-isolated IMCD demonstrated that L-arginine uptake by IMCD was significantly greater (663±100 pmol/mg/min, n=6) in rats exposed to a low sodium diet (0.4% NaCl) in comparison to rats on a normal (1% NaCl, 519±78 pmol/mg/min, n=6) or high sodium diet (4.0% NaCl, 302±27 pmol/mg/min, n=6). Immunoblotting experiments demonstrated that CAT1 immunoreactive protein was significantly decreased by approximately 30% in rats maintained on a high NaCl diet (n=5) compared to rats on a low NaCl diet (n=5). In contrast to the L-arginine transport and immunoblotting data, in vivo blockade of L-arginine uptake led to hypertension of equal magnitude in rats maintained on a low or high NaCl diet. These results indicate that sodium loading leads to a decrease in immunoreactive CAT1 protein in the rat renal medulla resulting in decreased L-arginine uptake capacity. The decrease in L-arginine uptake capacity, however, doesn't alter the blood pressure response to L-arginine uptake inhibition in the renal medulla.