Didier Doucet

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

&NA; Touati C, Idee J‐M, Deray G, Santus R, Balut C, Beaufils H, Jouanneau C, Bourbouze R, Doucet D, Bonnemain B. Modulation of the renal effects of contrast media by endotheliumderived nitric oxide in the rat. Invest Radiol 1993;28:814‐820. rationale and objectives. A possible involvement of endothelium derived relaxing nitric oxide (NO) in the pathogenesis of iodinated contrast media (CM)‐induced nephrotoxicity was investigated in the rat. methods. Male rats (6 to 12 per group) were uninephrectomized. Six days later, the aorta was clamped above the renal artery and a low‐osmolar contrast medium (CM), ioxaglate, was injected (1 mL/min; 3 minutes) via an aortic puncture in the single remaining kidney. Contrast medium was injected with or without the NO‐synthase inhibitor L‐NAME (100 mg/kg intravenously [IV] 5 minutes before CM). One group received L‐Arginine, the physiological precursor of NO (100 mg/kg IV), 5 minutes before L‐NAME. Phenylephrine (300 &mgr;g/kg; 30 min) was used as a vasoconstrictive NO‐independent control. The effects of iohexol, another low‐osmolar CM, on creatinine clearance (CrCl) were also studied with and without pretreatment with L‐NAME. A control group was subjected to a 3‐minute renal ischemia only. Creatinine clearance and urinary N‐acetyl‐beta‐D‐glucosaminidase (NAG) excretion were determined before, and 24 and 48 hours after CM administration. Blinded histologic analysis was carried out after completion of the study. results. When administered alone, neither L‐NAME nor L‐arginine modified CrCl. Ioxaglate mildly but significantly decreased CrCl at 24 hours (−26.5% of preinjection value). This was similar to the effect observed in the control group subjected to ischemia only. When associated with L‐NAME, ioxaglate markedly decreased CrCl (−58 + 11% at 24 hours, P < .05 vs. ioxaglate alone). A similar interaction was noted in the case of iohexol. L‐NAME also markedly increased ioxaglate‐induced urinary NAG excretion. Phenylephrine had a similar impact on renal function. L‐arginine pretreatment reduced the increase in serum creatinine induced by L‐NAME + ioxaglate (68 + 17 &mgr;mol/L vs. 175 + 59 &mgr;mol/L for L‐NAME + ioxaglate; P < .05) and urinary NAG excretion. Ioxaglate alone induced only tubular epithelial vacuolization. When associated with L‐NAME, this CM induced tubular and vascular lesions, as well as necrosis in the outer medulla. Such histologic effects were clearly inhibited by L‐arginine. conclusion. These data indicate that L‐NAME, a specific inhibitor of NO‐synthase, and phenylephrine, accentuate the nephrotoxicity of CM in the rat. This is consistent with results from the literature showing that CM‐toxicity is enhanced by renal ischemia.

Nitrogen-containing cyclic ligands, metallic complexes formed by these ligands, diagnostic compositions containing these complexes and process for the preparation of the ligands

The subject of the invention is nitrogen-containing cyclic ligands and metal complexes formed by these ligands, the uses of these complexes as magnetic resonance imaging (MRI) agents, as X-ray contrast agents and as chemical shift reagents in vivo.