The Role of Cationic Amino Acid Transporters in the Regulation of Blood Flow and Nitric Oxide in Rat Kidney
Previous studies from our laboratory have indicated that nitric oxide (NO) production by isolated inner medullary collecting duct cells is dependent on cellular uptake of L-arginine via cationic amino acid (CAT) transporters (FASEB J 13:A723,1999). In the present study we performed experiments to determine if CAT transport regulates NO production and renal hemodynamics in the renal medulla in vivo. The effects of renal medullary interstitial infusion of cationic amino acids (100 μg/kg/min) on renal medullary blood flow and NO levels were examined in anesthetized Sprague-Dawley rats by laser-Doppler flowmetry and a microdialysis-oxyhemoglobin trapping technique. Furthermore, we studied the effect of chronic intramedullary infusion of L-ornithine (50 μg/kg/min) on arterial pressure in uninephrectomized SD rats. Renal medullary blood flow was significantly reduced during the acute intramedullary infusion (30 min) of the cationic amino acids L-ornithine (-24±3%, N=4), L-lysine (-20±1%, N=4), and L-homoarginine (-21±2%, N=4), and during infusion of the NOS inhibitor Nω-nitro-L-arginine methyl ester (L-NAME; -38±4%, N=6). In contrast, infusion of L-arginine significantly increased medullary blood flow (+17±4%, N=4) and the neutral amino acids L-leucine, L-serine, and L-glycine (N=4 each) had no effect on renal medullary blood flow. NO concentration in the renal medulla was significantly decreased by the intramedullary infusion of L-ornithine (for 60 min; 336 ± 25 vs 232 ± 34 nmol/L, N=6, p<0.05). In contrast, NO concentration in renal cortex was not significantly affected by the intracortical infusion of L-ornithine (227 ± 31 vs 240 ± 60 nmol/L, p=NS). Similar changes in NO were observed with medullary and cortical infusion of L-lysine. Finally, chronic infusion of L-ornithine into the renal medulla of uninephrectomized SD rats for 7 days led to a sustained increase in mean arterial pressure (168±5 mmHg, N=5) when compared to vehicle treated rats (125±3 mmHg, N=6). These results suggest that CAT transport in the renal inner medulla may play an important role in the production of NO, the maintainence of blood flow, and the level of mean arterial pressure.