Renal vasoconstriction induced by oxidized LDL is inhibited by scavengers of reactive oxygen species and L-arginine

Background: Low density lipoprotein (LDL) may be involved in the pathogenes is of,glomerulosclerosis and progressive renal dysfunction associated with atherosclerotic renal artery stenosis (RAS), This study was undertaken to i nvestigate the effects of native (n-LDL) and oxidized LDL (ox-LDL) on renal vascular response and function in an isolated perfused rat kidney (IPRK) m odel. Material and method: IPRK model was used for the study at a constant pressure of 100 mm of HE in the renal artery with continuous monitoring of pressure and renal perfusate flow. Urine and perfusate samples were collect ed to determine [C-14] Inulin clearance and fractional reabsorption of sodi um. To elucidate the role of nitric oxide (NO) urinary c-GMP, nitrate and n itrite excretion were measured and the responses to the NO synthase inhibit or N-monomethyl-L-arginine (LNMMA) and the NO donor Nitrosoglutathione (GSN O) were assessed. The effect of L-arginine supplementation and the role of reactive oxygen species were also studied by adding superoxide dismutase (S OD) and catalase. Results: Ox-LDL but not n-LDL caused vasoconstriction in IPRK, as evidenced by a significant dose dependent reduction in renal perfu sate flow. [C-14] Inulin clearance and fractional reabsorption of sodium we re reduced during ox-LDL infusion whereas no significant change occured wit h n-LDL. There was a significant decrease in urinary excretion of c-GMP dur ing ox-LDL infusion. 10 mu M LNMMA significantly increased and GSNO (10 mu M) significantly diminished the vasoconstrictory effect of oxLDL. The prese nce of L-arginine (100 & 500 I-IM) significantly decreased ox-LDL induced v asoconstriction. SOD (150 U/ml) and catalase (1200 U/ml) both had a signifi cant inhibitory effect and the combination of SOD and catalase almost compl etely abolished the vasoconstriction due to ox-LDL. Conclusion: These resul ts suggest that ox-LDL induced vasoconstriction in IPRK is mediated by decr eased activity of NO probably due to inactivation of NO by reactive oxygen species. The free radical scavengers SOD, catalase and L-arginine provided protection against oxLDL induced vasoconstriction in this model.