Nitric oxide in ischaemic acute renal failure of streptozotocin diabetic rats.
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.
Goor
Y
Y
Department of Internal Medicine, Tel Aviv Medical Center, Israel.
Peer
G
G
Iaina
A
A
Blum
M
M
Wollman
Y
Y
Chernihovsky
T
T
Silverberg
D
D
Cabili
S
S
D058186:Acute Kidney Injury / Q000097:blood / Q000503:physiopathology*; D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D003404:Creatinine / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000097:blood / Q000503:physiopathology*; D007511:Ischemia / Q000503:physiopathology*; D009392:Nephrectomy; D009566:Nitrates / Q000097:blood / Q000652:urine; D009569:Nitric Oxide / Q000502:physiology*; D009573:Nitrites / Q000097:blood / Q000652:urine; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012077:Renal Artery; D012079:Renal Circulation; D012964:Sodium / Q000652:urine
D009566:Nitrates; D009573:Nitrites; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D012964:Sodium; D003404:Creatinine