Background:
In ischemic acute renal failure (arf), nitric oxide-dependent regulation of renal hemodynamics and glomerular function is disturbed. previous studies indicate that the nitric oxide precursor l-arginine (l-arg) has beneficial effects on renal function. here we further analyzed the impact of l-arg on functional and biochemical parameters of nitric oxide signaling during the course of ischemic arf.
Methods:
Ischemic arf was induced in rats by bilateral clamping of renal arteries for 45 minutes. l-arg was applied intraperitoneally during clamping, and orally during 14 days of follow-up. glomerular filtration rate (gfr) and renal plasma flow (rpf) were measured, and biochemical parameters analyzed by protein immunoblots.
Results:
Clamping resulted in 70% to 90% reduction of gfr and rpf, with a gradual recovery by day 14. using an in situ assay with the oxidative fluorescent dye hydroethidine, increased tubular generation of o2- was detected in the early course of ischemic arf, indicating enhanced oxidative stress. these findings were accompanied by up-regulation of the nitric oxide receptor, soluble guanylate cyclase, and by significant regulatory changes of inducible nitric oxide synthase (inos) and endothelial nos expression. l-arg had a beneficial effect on gfr and rpf, decreased o2- production, diminished up-regulation of soluble guanylate cyclase, and prevented up-regulation of inos.
Conclusion:
Ischemic arf is accompanied by marked alterations in the expression of key enzymes of the nitric oxide pathway, indicative for deficiency of constitutive nos activity. l-arg supplementation reduces o2- generation and significantly improves the expression of nitric oxide signaling proteins as well as the recovery phase of ischemic arf.