Time dependence of Na-nitroprusside administration in the prevention of neutrophil infiltration in the rat ischemic kidney.
The aim of this study was to determine the ideal time of administration of Na-nitroprusside to prevent neutrophil infiltration in ischemically damaged kidneys. Sprague-Dawley rats were subjected to 75 min of renal warm ischemia and contralateral nephrectomy. The animals were divided into 7 groups: the ischemic control (IC), which received normal saline, the sham group without warm ischemia and the experimental groups, which received intravenous Na-nitroprusside (NP) (5 mg/kg) at 75, 30, 15, and 5 min prior to reperfusion. Another experimental group was given verapamil (V) (5 mg/kg) as a NO-independent vasodilator 5 min prior to reperfusion. The final evaluation included survival at seven days, serum creatinine (SCr) and blood urea nitrogen (BUN) daily for 3 days, and neutrophil infiltration determined by the presence of myeloperoxidase (MPO) in renal tissue at 2 hr after reperfusion. Histological damage was assessed at 24 hr. There were significant improvements in all parameters when the Na-NP was administered at 75, 30, and 15 min prior to reperfusion when compared with the control group (p < 0.05). There were no differences either in survival or renal function when the 5 min group was compared with the IC or V groups. It is concluded then, that Na-NP can be administered as late as 15 min before reperfusion and still have a protective effect. It appears that the mechanism of protection of Na-NP is due to blocking of one of the steps of the interaction between leukocytes and endothelium--migration. Furthermore, the verapamil (a NO-independent vasodilator) and Na-NP5 (a NO-dependent vasodilator) groups did not show a beneficial effect in these severely ischemically damaged kidneys, which might be one more reason to believe that Na-NP could be interacting at the level of leukocyte-endothelial cell interaction.
Lopez-Neblina
F
F
Borgess Medical Center, Department of Biological Sciences, Western Michigan University, Kalamazoo 49001, USA.
Toledo-Pereyra
L H
LH
Mirmiran
R
R
Paez-Rollys
A J
AJ
D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D007511:Ischemia / Q000473:pathology*; D007668:Kidney / Q000098:blood supply* / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology*; D009569:Nitric Oxide / Q000008:administration & dosage; D009599:Nitroprusside / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D009599:Nitroprusside; D009569:Nitric Oxide