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 pathogenesis of glomerulosclerosis and progressive renal dysfunction associated with atherosclerotic renal artery stenosis (RAS). This study was undertaken to investigate the effects of native (n-LDL) and oxidized LDL (ox-LDL) on renal vascular response and function in an isolated perfused rat kidney (IPRK) model.

MATERIAL AND METHOD

IPRK model was used for the study at a constant pressure of 100 mm of Hg in the renal artery with continuous monitoring of pressure and renal perfusate flow. Urine and perfusate samples were collected to determine [14C] Inulin clearance and fractional reabsorption of sodium. To elucidate the role of nitric oxide (NO) urinary c-GMP, nitrate and nitrite excretion were measured and the responses to the NO synthase inhibitor N-monomethyl-L-arginine (LNMMA) and the NO donor Nitroso-glutathione (GSNO) were assessed. The effect of L-arginine supplementation and the role of reactive oxygen species were also studied by adding superoxide dismutase (SOD) and catalase.

RESULTS

Ox-LDL but not n-LDL caused vasoconstriction in IPRK, as evidenced by a significant dose dependent reduction in renal perfusate flow. [14C] Inulin clearance and fractional reabsorption of sodium were reduced during ox-LDL infusion whereas no significant change occured with n-LDL. There was a significant decrease in urinary excretion of c-GMP during ox-LDL infusion. 10 microM LNMMA significantly increased and GSNO (10 microM) significantly diminished the vasoconstrictory effect of ox-LDL. The presence of L-arginine (100 & 500 microM) significantly decreased ox-LDL induced vasoconstriction. SOD (150 U/ml) and catalase (1200 U/ml) both had a significant inhibitory effect and the combination of SOD and catalase almost completely abolished the vasoconstriction due to ox-LDL.

CONCLUSION

These results suggest that ox-LDL induced vasoconstriction in IPRK is mediated by decreased 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 ox-LDL induced vasoconstriction in this model.