[Nitric oxide (NO) in a model of renal ischemia and cyclosporine toxicity].
BACKGROUND
The role of nitric oxide (NO) after the cadaveric kidney transplantation has not been fully clarified yet. The aim of our study was to examine benefits of the administration of a NO precursor--L-arginine in the model of renal ischaemia and after the subsequent cyclosporine (CsA) treatment, which simulates the state resulting from the kidney transplantation.


RESULTS
60 male rats of the Wistar strain were exposed to ischaemia for 45 minutes. Then they were divided into six groups: 1. Controls, 2. Rats administered by gastric sonde with 300 mg/kg of L-arginine since the first day after ischaemia, 3. Rats administered in a similar way with 10 mg/kg of cyclosporine A, 4. Group of rats receiving both drugs in the same doses, 5. Rats receiving 10 mg/kg of cyclosporine A since the first day after ischaemia and L-arginine in the dose 300 mg/kg since the seventh day, 6. Group of animals administered with L-arginine and cyclosporin A in the same doses with nonselective blocker of NO synthesis--L-NNA in the dose of 5 mg/kg. We examined renal functions (blood and urine levels of creatinine, urea, Na, K, Cl, osmolality, proteinuria), blood and urine levels of NO metabolites (NO2- and NO3-) in the fourth week after ischaemia. We found that L-arginine administration (when groups 1 and 2 were compared) decreased S-creatinine (< 0.05), it increased U-osmolality (p < 0.01), tubular resorption (p < 0.001), and blood levels of NO metabolites (p < 0.05). Changes in urine levels of NO metabolites (U-NOx/U-Cr) and in proteinuria were not found. In animals with renal ischaemia treated with cyclosporine (comparison of groups 3 and 4), L-arginine administration brought about a decrease of blood creatinine levels (p < 0.05), higher creatinine clearance (p < 0.05) and higher blood levels of NO metabolites (S-NOx; p < 0.01). However, differences in tubular functions, proteinuria and U-NOx/U-Cr were not detected. When L-arginine was added 7 days after the beginning of cyclosporine treatment, no significant difference was found between groups 5 and 3 and differences between groups 5 and 4 were similar to those between groups 4 and 3. Animals of the group 6 were not tested due to high mortality indicating high toxicity of the combination ischaemia + cyclosporine + L-arginine + L-NNA.


CONCLUSIONS
Our study shows the benefits of L-arginine treatment in the renal ischaemia and during cyclosporine administration. The treatment should start immediately after the ischaemic period and at the same time as the cyclosporine administration. L-arginine added later has no positive effect.
Bubenícek
P
P
Klinika nefrologie a Metabolické pracovistĕ, Institut klinické a experimentální medicíny, Praha. petr.bubenicek@medicon.cz
Kazdová
L
L
Bohdanecká
M
M
Táborský
P
P
Veselá
J
J
Skibová
J
J
Matl
I
I
Teplan
V
V
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D016572:Cyclosporine / Q000633:toxicity*; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007511:Ischemia / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D014665:Vasodilator Agents; D009569:Nitric Oxide; D016572:Cyclosporine; D001120:Arginine
Oxid dusnatý (NO) u modelu ischémie ledvin a cyklosporinové toxicity.