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 mumol/kg/min; 30 min) and subsequent super-imposition of L-arginine (100 mumol/kg/min; 30 min), the NO synthase inhibitor, N(G)-nitro-L-arginine (2.4 mg/kg; i.v bolus) and the NO donor sodium nitroprusside (0.24 mug/kg/min) 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 superimposition of L-arginine reversed these effects of L-lysine in SD rats. In SHR, L-lysine and subsequent super-imposition 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-(3)H-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.
Rajapakse, N. W., Kuruppu, D. M. S., Hanchapola, I., Venardos, K. M., Mattson, D. L., Smith, A. I., Kaye, D. M., & Evans, R. G. (2012). Evidence that renal arginine transport is impaired in spontaneously hypertensive rats. American Journal of Physiology-Renal Physiology, 302(12), F1554 - F1562. https://doi.org/10.1152/ajprenal.00084.2011