Southern Association for Vascular surgery
October 15, 2007

The Role of Apoptosis on the Mechanisms(s) of Contrast-Induced Nephropathy in a Genetic Rat Model of Type II Diabetes and Obesity

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

The Effect of Diabetes on Contrast-Induced Apoptosis on the Renal Medulla and Cortex
Groups Lean/Saline Lean/Conray fa/fa/Saline fa/fa/Conray
Caspace 8 (14 Kd)
Cortex		 171+/-22 146+/-16 121+/-15 95+/-12
Caspace 8 (14 Kd)
Medulla		 206+/-36 246+/-21 239+/-52 391+/-34a,b,c
Caspace 8 (42 Kd)
Cortex		 1316+/-83 1191+/-58 1078+/-21 1310+/-31c
Caspace 8 (42 Kd)
Medulla		 883+/-116 1003+/-98 939+/-108 1280+/-93c
P38-MAPK
Cortex		 93+/-7 94+/-7 70+/-6 75+/-4
P38-MAPK
Medulla		 190+/-8 148+/-15 131+/-19 143+/-8

Background: We have utilized the Zucker (fa/fa) rat (a genetic model of Type II diabetes and obesity) to show that diabetes exaggerates contrast-induced nephropathy (CIN) when compared to the genetic control (Zucker lean). The mechanism of the diabetes-induced exaggerated CIN is unknown. This study examines the hypothesis that early cell death (apoptosis) is one of the mechanism(s) that contributes to the marked increase in CIN in the diabetic.METHODS:Anesthetized male Zucker (fa/fa) and Zucker (lean) rats (10 weeks old) either had an infusion of saline or Conray 400 (6 mls/kg, ionic contrast, Mallinckrodt Chem.). Sixty minutes later the kidneys were removed and separated into the renal cortex and medulla. The proteins were separated and analyzed for Caspace 8 (Ca-8) at 42/44 kilodaltons (C8-42) or 14 Kd (C8-14) and P38-MAP-kinase (P38) content by Western Blot Analysis. The blots were objectively analyzed by Densitometry and reported as Mean. ± SEM (N≥5, p< 0.05 by ANOVA when compared to the Lean-Saline group (a), Lean-Conray group. (b) and fa/fa-Saline group (c).
Results: Conray 400 induced a marked increase in Caspace 8 42/44 Kd in the cortex and medulla and induced an increase in Caspace 8 14 Kd in the medulla in the Zucker (fa/fa) that was not found in the lean control.
Conclusions: These data suggest that a single exposure to the ionic contrast agent Conray 400 induced early apoptotic changes in the Zucker (fa/fa) rat. These data suggest that CIN is due in part from apoptosis which is exaggerated in this rat model of Type II Diabetes and obesity.
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