An Angiotensin Converting Enzyme Inhibitor Suppresses Contrast Media Induced Renal Dysfunction in a Murine Model of Subtotal Nephrectomy

Abstract

Backgrounds: Contrast media (CM)-induced nephropathy (CIN) affects morbidity and mortality in humans. Although CIN is mediated by several factors including the renin-angiotensin system (RAS), little is known about the pathophysiology. To clarify the mechanism, we developed a novel murine CIN model. Methods: We made 5/6 subtotal nephrectomy (NTX) and administered CM (iopamidol) intravenously into the mice 4 weeks after NTX. Mice received an angiotensin converting enzyme inhibitor (ACEI, n=6), an angiotensin II receptor blocker (ARB, n=4), or ACEI plus a bradykinin B2 receptor antagonist (Hoe-140, n=5) daily. Results: Serum creatinine levels were significantly elevated in the NTX group compared to the non-NTX group on day 28. A day after CM injection, creatinine levels were additionally elevated in the non-treated group. While ACEI treatment significantly suppressed the creatinine levels, ARB treatment did not decrease the levels. Hoe-140 negated ACEI’s ability to suppress renal dysfunction. Conclusion: ACEI treatment may be useful for the prevention of CM-induced nephropathy. Keywords: Angiotensin converting enzyme, bradykinin, contrast media, murine model, renal dysfunction, renin angiotensin system.