Evidence that renal arginine transport is impaired in spontaneously hypertensive rats

Low renal nitric oxide (NO) bioavailability contributes to the development and maintenance of chronic hypertension. We investigated whether impaired L-arginine transport contributes to low renal NO bioavailability in hypertension. Responses of renal medullary perfusion and NO concentration to renal arterial infusions of the L-arginine transport inhibitor L-lysine (10 μmol·kg^-1·min^-1; 30 min) and subsequent superim-position of L-arginine (100 μmol·kg^-1·min^-1; 30 min), the NO synthase inhibitor N ^G-nitro-L-arginine (2.4 mg/kg; iv bolus), and the NO donor sodium nitroprusside (0.24 μg·kg^-1·min^-1) were examined in Sprague-Dawley rats (SD) and spontaneously hypertensive rats (SHR). Renal medullary perfusion and NO concentration were measured by laser-Doppler flowmetry and polarographically, respectively, 5.5 mm below the kidney surface. Renal medullary NO concentration was less in SHR (53 ± 3 nM) compared with SD rats (108 ±12 nM; P = 0.004). L-Lysine tended to reduce medullary perfusion (- 15 ± 7%; P = 0.07) and reduced medullary NO concentration (- 9 ± 3%; P = 0.03) while subsequent super imposition of L-arginine reversed these effects of L-lysine in SD rats. In SHR, L-lysine and subsequent superimposition of L-arginine did not significantly alter medullary perfusion or NO concentration. Collectively, these data suggest that renal L-arginine transport is impaired in SHR. Renal L-[³H]arginine transport was less in SHR compared with SD rats (P = 0.01). Accordingly, we conclude that impaired arginine transport contributes to low renal NO bioavailability observed in the SHR kidney.