RENAL MEDULLARY INTERSTITIAL INFUSION OF L-ARGININE PREVENTS HYPERTENSION IN DAHL SALT-SENSITIVE RATS

Studies were designed to examine the effects of renal medullary inters titial infusion of L-arginine (L-Arg) on the development of high-salt- induced hypertension in Dahl salt-sensitive/Rapp (DS) rats. The thresh old dose of L-Arg (300 mu g . kg(-1). min(-1)) that increased the rena l medullary blood flow without altering the cortical blood flow was fi rst determined in anesthetized DS rats. Studies were then carried out to determine the effects of this dose of L-Arg on salt-induced hyperte nsion in DS rats. In the absence of chronic medullary L-Arg infusion, mean arterial pressure (MAP) increased in DS rats from 125 +/- 2 to 16 7 +/- 5 mmHg by day 5 of a high-salt diet (4.0%), with no change obser ved in Wistar-Kyoto (WKY) or Dahl salt-resistant/Rapp (DR) rats. MAP d id 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 inf used into the renal medulla (300 mu g . kg(-1) . min(-1)) failed to bl unt salt-induced hypertension when administered intravenously to DS ra ts. DS rats receiving L-Arg (300 mu g . kg(-1) . min(-1) iv) exhibited an increase in plasma L-Arg from control concentrations of 138 +/- 11 to 218 +/- 4 mu mol/l, while MAP, which averaged 124 +/- 3 mmHg durin g the 3-day control period, rose to 165 +/- 5 mmHg by clay 5 of high s alt (4%) intake. These results indicate that the prevention of salt se nsitivity in DS rats was due specifically to the action of L-Arg on re nal medullary function and that DS rats may have a deficit of medullar y substrate availability and NO production.