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Iodinated Contrast Induced Renal injury is exaggerated in A rat model of genetic non-insulin-dependent-diabetes mellitus and Obesity

Stuart I Myers¹, Li Wang², Daniel J Myers^.3
1University of Tennessee, Chattanooga Campus, Chattanooga,, TN; ²McGuire Veterans Research Corporation, Richmond, VA; ³Johns Hopkins University, Baltimore, MD.

OBJECTIVES: The mechanism of the increased risk of contrast-induced nephropathy in diabetic patients is unknown. This study examines the hypothesis that the contrast-induced decrease in renal microvascular blood flow and function is markedly exaggerated in a rat genetic model of obesity and NIDDM (Zucker (fa/fa)) compared to the genetic control (Zucker lean).

METHODS:Anesthetized male Zucker (fa/fa) and Zucker (lean) rats (10 weeks old) either had micro-dialysis probes or Laser Doppler fibers inserted into the renal cortex (2mm) and renal medulla (4mm). The microdialysis probes were perfused in vivo at 3 μl/min with the dialysate assayed for total NO (uM), PGE2, 6-keto-PGF1a (PGI2) and thromboxane B2 (TxB2) synthesis at time zero (Basal) and following infusion of saline or Conray 400 (6 mls/kg, ionic contrast, Mallinckrodt Chem). Both groups were treated with either carrier or Superoxide dismutase (SOD, 10,000 u/kg, ODFR scavenger) The renal cortex and medulla were analyzed for iNOS, COX-2, Prostacyclin Synthase (PS) and PGE2 synthase content by Western Blot. Creatinine clearance was calculated as mls/min and all other data reported as percent of basal (Mean. ± SEM, N≥6, p< 0.05 by ANOVA)..

RESULTS:Conray decreased creatinine clearance by 60% in the Lean group compared to an 80% decrease in the fa/fa group (p<0.01). Medullary PS content was increased in the Lean/Conray group by 100% whereas it was decreased by 50% in the fa/fa/Conray group (p<0.05). Cortical COX-2 content was increased in the Lean/Conray group by 50% whereas it was decreased by 50% in the fa/fa/Conray group (p<0.05). Only minor changes were noticed in the content of iNOS, PGE2 synthase and PGE2 synthesis.

CONCLUSIONS: Conray caused a 2-fold or greater decrease in renal function and cortical and medullary blood flow in the Zucker (fa/fa) compared to the Lean control. The Lean rats responded to the renal injury by increasing cortical and medullary PGI2 synthesis and content of PS. Conray induced a marked increase in cortical and medullary TxB2 synthesis in the Zucker (fa/fa) group. The marked differences in the renal cortical and medullary synthesis of the potent vasoconstrictor TxB2 and the potent vasodilator PGI2 may in part be one of the mechanisms contributing to decreased microvascular blood flow and renal function in this model of NIDDM and obesity.