Nitric oxide metabolism following unilateral renal ischemia/reperfusion injury in rats

Abstract.

Renal ischemia/reperfusion (I/R) injury results in decreased glomerular filtration and renal blood flow (RBF) and increased urine output, characterized by natriuresis and impaired concentrating ability. We studied unilateral I/R in rats to assess renal handling of nitric oxide (NO). Prior to I/R, we measured urine flow rate (V), inulin clearance (C _IN), para-aminohippuric acid clearance (C _PAH), NO clearance (C _NOx determined from metabolites NO₂ and NO₃), tubular transport of NO_x (T_NOx, filtered load ± urinary excretion), urine sodium and potassium excretion (U_NaV, U_KV), fractional excretion of sodium (FENa), and fractional excretion of NO_x (FENO_x) in each kidney. The left renal artery was then ligated for 30 min, followed by 30 min of reperfusion, and all measurements were repeated. C _IN and C _PAH were decreased in I/R kidneys compared with the contralateral kidney or pre-ischemia controls. V, FENa, and U_KV were all significantly increased in I/R kidneys. Plasma NO_x concentration was lower after injury in all animals (23.3±2.8 post injury vs. 30.4±7.7 μM pre injury, P <0.05). C _NOx was significantly higher in I/R kidneys (0.14±0.05 ml/min per g kidney weight) than in pre-injury kidneys (0.03±0.02 right, 0.04±0.30 left) or the contralateral controls (0.04±0.02) (P <0.05 for all three controls). T_NOx showed net tubular reabsorption of NO_x in all kidneys (11±6 in post-ischemic left kidneys vs. 25±20 in left pre-ischemia, 33±13 in right pre-ischemia, and 21±4 right post-ischemia, nM/min per g kidney weight, P = NS). FENO_x was higher in injured kidneys (28%±18) than in pre-injury (3%±0.6, 5%±3) or contralateral controls (6%±3) (P <0.05 for all three controls). Renal NO_x excretion and clearance are increased despite decreased plasma levels of NO metabolites after I/R injury. This increased excretion is not dependent on RBF or glomerular filtration, but may be related to impaired tubular reabsorption of NO_x combined with increased intra-renal NO production.