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 x mg(-1) x 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 x mg(-1) x min(-1), n = 6) or high-sodium diet (4.0% NaCl, 302 +/- 27 pmol x mg(-1) x min(-1), 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 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.
D000818:Animals; D001120:Arginine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D027201:Cationic Amino Acid Transporter 1 / Q000378:metabolism; D004032:Diet; D004305:Dose-Response Relationship, Drug; D007679:Kidney Medulla / Q000166:cytology / Q000378:metabolism*; D008239:Lysine / Q000494:pharmacology; D008297:Male; D009952:Ornithine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000008:administration & dosage*
D027201:Cationic Amino Acid Transporter 1; D012965:Sodium Chloride; D001120:Arginine; D009952:Ornithine; D008239:Lysine