Modulation of the renal effects of contrast media by endothelium-derived nitric oxide in the rat.

摘要: RATIONALE AND OBJECTIVES: A possible involvement of endothelium derived relaxing nitric oxide (NO) in the pathogenesis iodinated contrast media (CM)-induced nephrotoxicity was investigated rat. METHODS: Male rats (6 to 12 per group) were uninephrectomized. Six days later, aorta clamped above renal artery and a low-osmolar medium (CM), ioxaglate, injected (1 mL/min; 3 minutes) via an aortic puncture single remaining kidney. Contrast with or without NO-synthase inhibitor L-NAME (100 mg/kg intravenously [i.v.] 5 minutes before CM). One group received L-Arginine, physiological precursor NO i.v.), L-NAME. Phenylephrine (300 micrograms/kg; 30 min) used as vasoconstrictive NO-independent control. The effects iohexol, another CM, on creatinine clearance (CrCl) also studied pretreatment control subjected 3-minute ischemia only. Creatinine urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion determined before, 24 48 hours after CM administration. Blinded histologic analysis carried out completion study. RESULTS: When administered alone, neither nor L-arginine modified CrCl. Ioxaglate mildly but significantly decreased CrCl at (-26.5% preinjection value). This similar effect observed associated L-NAME, ioxaglate markedly (-58 + 11% hours, P < .05 vs. alone). interaction noted case iohexol. increased ioxaglate-induced NAG excretion. had impact function. reduced increase serum induced by L-NAME+ioxaglate (68 17 mumol/L 175 59 for L-NAME+ioxaglate; .05) alone only tubular epithelial vacuolization. this vascular lesions, well necrosis outer medulla. Such clearly inhibited L-arginine. CONCLUSION: These data indicate that specific NO-synthase, phenylephrine, accentuate is consistent results from literature showing CM-toxicity enhanced ischemia.