Protective effect of L-arginine on hypercholesterolemia-enhanced renal ischemic injury.
The effects of hypercholesterolemia on ischemic renal failure were evaluated in rats subjected to 60 min of left renal artery clamping and contralateral nephrectomy. One group of rats (HC) was kept on a cholesterol-supplemented diet for 3 weeks before renal injury and compared to a group fed a regular diet (ND). Two days after renal ischemia, inulin clearance (C(in), ml/min per 100 g BW) was lower in HC-rats (0.033 +/- 0.011) than in ND-rats (0.227 +/- 0.037; P < 0.01). indicating that hypercholesterolemia potentiated renal ischemic injury. Twenty-one days after renal ischemia the C(in) of HC-rats did not differ from ND-rats, suggesting that hypercholesterolemia did not limit late recovery. Since nitric oxide production is impaired in HC, L-arginine (50 mg/kg BW i.v.) was administered immediately after ischemia. Two days after ischemia, L-arg did not protect ND-rats from ischemia, while the C(in) and renal blood flow were higher in L-arg-treated HC rats than in untreated HC rats (C(in) = 0.125 +/- 0.013 rats vs. 0.033 +/- 0.011; P < 0.001) (RBF = 3.96 +/- 0.64 vs. 2.40 +/- 0.20 ml/min per 100 g BW; P < 0.05), indicating that L-arg protects HC rats from renal ischemia. The administration of D-arginine to ND rats induced a significant decrease of the C(in) and a significant increase of FE H2O, FE Na and FE K compared to the L-arginine and not treated groups. Cultures of inner medullary collecting duct cells from ND rats were resistant to 24-h hypoxia. In contrast, IMCD cell cultures from HC rats showed higher LDH release after 24-h hypoxia than normoxic cells (69.2 +/- 3.4 vs. 30.9 +/- 3.6%, P < 0.001); 1 mM L-arg added to the medium attenuated LDH release (44.3 +/- 2.4%, P < 0.01). These data demonstrate that HC predisposes renal tubular cells to hypoxic injury and L-arg protects cells of HC.
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Laboratório de Pesquisa Básica da Disciplina de Nefrologia da Faculdade de Medicina da Universidade de São Paulo, Brazil.
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D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000009:adverse effects; D004195:Disease Models, Animal; D006937:Hypercholesterolemia / Q000150:complications / Q000378:metabolism*; D007668:Kidney / Q000098:blood supply*; D007677:Kidney Function Tests; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000032:analysis / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects
D002791:Cholesterol, Dietary; D009569:Nitric Oxide; D001120:Arginine; D007770:L-Lactate Dehydrogenase