Renal medullary interstitial infusion of L-arginine prevents hypertension in Dahl salt-sensitive rats

Studies were designed to examine the effects of renal medullary interstitial infusion of L-arginine (L-Arg) on the development of high-salt- induced hypertension in Dahl salt-sensitive/Rapp (DS) rats. The threshold dose of L-Arg (300 μg · kg^-1 · min^-1) that increased the renal medullary blood flow without altering the cortical blood flow was first determined in anesthetized DS rats. Studies were then carried out to determine the effects of this dose of L-Arg on salt-induced hypertension in DS rats. In the absence of chronic medullary L-Arg infusion, mean arterial pressure (MAP) increased in DS rats from 125 ± 2 to 167 ± 5 mmHg by day 5 of a high-salt diet (4.0%), with no change observed in Wistar-Kyoto (WKY) or Dahl salt-resistant/Rapp (DR) rats. MAP did not change significantly with medullary infusion of L-Arg alone in DR rats (control = 104 ± 1 mmHg) or in WKY rats (control = 120 ± 3 mmHg) and was not significantly changed from these levels during the 7 days of L-Arg infusion combined with high-NaCl diet. The same amount of L-Arg that prevented salt-induced hypertension in DS rats when infused into the renal medulla (300 μg · kg^-1 · min^-1) failed to blunt salt-induced hypertension when administered intravenously to DS rats. DS rats receiving L-Arg (300 μg · kg^-1 · min^-1 iv) exhibited an increase in plasma L-Arg from control concentrations of 138 ± 11 to 218 ± 4 μmol/l, while MAP, which averaged 124 ± 3 mmHg during the 3-day control period, rose to 165 ± 5 mmHg by day 5 of high salt (4%) intake. These results indicate that the prevention of salt sensitivity in DS rats was due specifically to the action of L-Arg on renal medullary function and that DS rats may have a deficit of medullary substrate availability and NO production.