Abstract 11417: An Angiotensin Converting Enzyme Inhibitor Suppresses Contrast Media Induced Renal Dysfunction via Bradykinin Pathway in a Murine Model of Subtotal Nephrectomy
Background: Iodinated contrast media (CM) has been used for diagnostic procedures; CM-induced nephropathy (CIN) affects morbidity and mortality of patients. Although CIN is mediated by several factors, including the renin-angiotensin system (RAS), little is known about the evidence obtained from experimental models. Hypothesis: We assessed the hypothesis that RAS could play a critical role in the progression of CIN.
Methods: We performed 5/6 subtotal nephrectomy (NTX) and administered CM (iopamidol) intravenously into the mice 4 weeks after NTX. We administered an angiotensin converting enzyme inhibitor (ACEI, imidapril, 1mg/kg/day, n=6), an angiotensin II receptor blocker (ARB, TA-606, 1mg/kg/day, n=4), or ACEI plus a bradykinin B2 receptor antagonist (Hoe-140, 0.25mg/kg, n=5) into the mice daily.
Results: Serum creatinine levels on day 28 were significantly elevated in the NTX group (0.26±0.01mg/dl) compared to those in the non-NTX group (0.13±0.01mg/dl). A day after CM injection, creatinine levels were additionally elevated in the non-treated group (0.41±0.01mg/dl). While ACEI treatment significantly suppressed the creatinine levels (0.34±0.04 mg/dl, p<0.05 vs. CIN group), ARB treatment did not suppress decrease the creatinine levels (0.47±0.06mg/dl). A bradykinin antagoninst Hoe-140 negated (0.43±0.07mg/dl, p<0.05 vs. CIN+ACEI) ACEI's ability to suppress renal dysfunction. AT1R mRNA levels were enhanced in the CIN group compared to those in the native group. COX-2, MCP-1 and MMP-9 mRNA levels were enhanced in CIN+ACEI group compared to the native and CIN groups, while ACEI+Hoe-140 treatment suppressed these mRNA expression. The transcription level of bradykinin was elevated in the ACEI-treated CIN kidneys, while Hoe-140 suppressed the level. ARB did not significantly affect the level. Both treatments did not reduce their blood pressure compared to those of the vehicle treatment, statistically.
Conclusion: ACEI treatment is useful for the prevention of CM-induced nephropathycompared to that of ARB treatment in the murine model of CIN because bradykinin pathway is critical to regulate CIN development.
- © 2011 by American Heart Association, Inc.