title: Evidence that renal arginine transport is impaired in spontaneously hypertensive rats.
abstract: 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 superimposition 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 superimposition 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-[(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.
authors.affiliation: Department of Physiology, Monash University, Melbourne, Australia. niwanthi.rajapakse@bakeridi.edu.au
authors.forename: N W
authors.initials: NW
authors.lastname: Rajapakse
authors.forename: S
authors.initials: S
authors.lastname: Kuruppu
authors.forename: I
authors.initials: I
authors.lastname: Hanchapola
authors.forename: K
authors.initials: K
authors.lastname: Venardos
authors.forename: D L
authors.initials: DL
authors.lastname: Mattson
authors.forename: A I
authors.initials: AI
authors.lastname: Smith
authors.forename: D M
authors.initials: DM
authors.lastname: Kaye
authors.forename: R G
authors.initials: RG
authors.lastname: Evans
mesh_terms: D000818:Animals; D001120:Arginine / Q000378:metabolism*; D001692:Biological Transport; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000378:metabolism*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D008239:Lysine / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology
chemical_list: D009599:Nitroprusside; D009569:Nitric Oxide; D001120:Arginine; D008239:Lysine