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Immunology‚ Endocrine & Metabolic Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Immunology‚ Endocrine and Metabolic Agents)
ISSN (Print): 1871-5222
ISSN (Online): 1875-5844
VOLUME: 13
ISSUE: 3
DOI: 10.2174/18715222113139990010      Price:  $58









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

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Author(s): Masahito Ogawa, Jun-ichi Suzuki and Mitsuaki Isobe
Pages 176-184 (9)
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.
Affiliation:
Department of Advanced Clinical Science and Therapeutics, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.