Influence of dietary NaCl on L-arginine transport in the renal medulla

Previous work demonstrated that L-arginine, the substrate for nitric oxide (NO) 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^-1· min^-1, n = 6) in rats exposed to a low-sodium diet (0.4% NaCl) compared with rats on a normal (1% NaCl, 519 ± 78 pmol·mg ^-1·min^-1, n = 6) or high-sodium diet (4.0% NaCl, 302 ± 27 pmol·mg^-1·min^-1, n = 6). Immunoblotting experiments demonstrated that CAT1 immunoreactive protein was significantly decreased by ∼30% in rats maintained on a high-NaCl diet (n = 5) compared with 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, does not alter the blood pressure response to L-arginine uptake inhibition in the renal medulla.