• Transplant. Proc. · May 2014

    Comparative Study

    Inhibition of inducible nitric oxide synthase ameliorates myocardial ischemia/reperfusion injury - induced acute renal injury.

    • T-H Chen, F-T Liao, Y-C Yang, and J-J Wang.
    • Division of Cardiovascular Surgery, Cathay General Hospital, Taipei, Taiwan.
    • Transplant. Proc. 2014 May 1; 46 (4): 1123-6.

    ObjectivesAcute kidney injury occurs frequently in patients subsequent to coronary artery revascularization or myocardial ischemia and reperfusion (MIR). Hypotension and excessive nitric oxide (NO) production through inducible nitric oxide synthase (iNOS) were implicated in renal injury. On the other hand, NO may have a protective role during early reperfusion. In this study, we aim to compare protective effectiveness of 1,400W, a highly selective iNOS inhibitor, and L-NG-nitroarginine methyl ester (L-NAME), a non-specific nitric oxide synthase (NOS) inhibitor, against MIR-induced hemodynamic stabilization and kidney injury.MethodsMale Sprague-Dawley rats were evenly divided in four groups including sham-operated, MIR, and groups pretreated with 1,400W (20 mg/kg, intraperitoneally, [ip]) or L-NAME (30 mg/kg, ip) 15 minutes before MIR. Ischemia was conducted by occluding the left coronary artery for 30 minutes, followed by 120 minutes of reperfusion. We determined the measured aortic pressure (MAP) and assessed kidney injury through serum levels of blood urea nitrogen (BUN), methylguanidine (MG), malondialdehyde (MDA) and NO at different phases during the study.ResultsMAP, decreased during myocardial ischemia, increased during early reperfusion; however, that was abolished with L-NAME pretreatment, and the increase was moderate with 1,400W pretreatment. Serum MDA, MG and BUN levels, although relatively unaltered during ischemia, significantly increased after 120 minutes of reperfusion. Treatment with 1,400W reduced post-reperfusion MDA and MG levels (P < .05), but the improvement was not significant with L-NAME.Conclusions1,400W was effective in reducing MIR-induced hemodynamic instability and kidney injury, in contrast to no apparent protection with L-NAME administration.Copyright © 2014 Elsevier Inc. All rights reserved.

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