Nitric oxide in ischaemic acute renal failure of streptozotocin diabetic rats

Diabetologia. 1996 Sep;39(9):1036-40. doi: 10.1007/BF00400651.

Abstract

Changes in nitric oxide (NO) levels were determined in ischaemic acute renal failure in streptozotocin-induced diabetes mellitus rats. Two weeks after streptozotocin administration and immediately after right nephrectomy, the left renal artery was occluded for 60 min. Similar procedures were carried out in non-diabetic rats. The nitrite (NO2) + nitrate (NO3) levels were measured in plasma and urine. The effects of chronic oral supplementation with L-arginine and an NO synthase inhibitor (N-omega-nitro-L-arginine) were also studied in both diabetic and non-diabetic rats before and after renal artery clamping. The rats with diabetic acute renal failure had a much lower creatinine clearance (90 +/- 22 microliters.min-1. 100g body weight-1, p < 0.005), and higher fractional excretion of sodium (FENa)% (10.90 +/- 4.2, p < 0.001) and protein excretion (2078 +/- 69 micrograms/ml creatinine clearance, p < 0.001) compared with the respective values in the non-diabetic groups (163 +/- 30; 1.46 +/- 86; 453.3 +/- 31). The plasma and urine NO2 + NO3 levels were significantly higher in the untreated diabetic rats compared with the untreated normal rats before ischaemia (p < 0.001). The ischaemic acute renal failure in non-diabetic rats increased the plasma and urinary NO2 + NO3 excretion after ischaemia. The urinary excretion of these metabolites decreased significantly and their plasma levels remained unchanged in the ischaemic diabetic rats. The L-arginine administration resulted in a small but significantly higher creatinine clearance after clamping in the non-diabetic rats. The NO synthase inhibitor caused deterioration in renal function in all ischaemic and non-ischaemic groups. In summary, the greater vulnerability to ischaemia of the diabetic kidney seems to be associated with both impaired response to and impaired production of NO.

Publication types

  • Comparative Study

MeSH terms

  • Acute Kidney Injury / blood
  • Acute Kidney Injury / physiopathology*
  • Analysis of Variance
  • Animals
  • Arginine / pharmacology
  • Creatinine / metabolism
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / physiopathology*
  • Diabetic Nephropathies / blood
  • Diabetic Nephropathies / physiopathology*
  • Ischemia / physiopathology*
  • Nephrectomy
  • Nitrates / blood
  • Nitrates / urine
  • Nitric Oxide / physiology*
  • Nitrites / blood
  • Nitrites / urine
  • Nitroarginine / pharmacology
  • Rats
  • Rats, Wistar
  • Reference Values
  • Renal Artery
  • Renal Circulation*
  • Sodium / urine

Substances

  • Nitrates
  • Nitrites
  • Nitroarginine
  • Nitric Oxide
  • Arginine
  • Sodium
  • Creatinine