• Life sciences · Nov 2014

    Potential amelioration of upregulated renal HIF-1alpha-endothelin-1 system by landiolol hydrochloride in a rat model of endotoxemia.

    • Yoshiyasu Ogura, Subrina Jesmin, Naoto Yamaguchi, Masami Oki, Nobutake Shimojo, Md Majedul Islam, Tanzila Khatun, Junko Kamiyama, Hideaki Sakuramoto, Keiichi Hagiya, Satoru Kawano, and Taro Mizutani.
    • Department of Emergency and Critical Care Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan; Center for Health Science, Ibaraki Prefectural University, Ami, Ibaraki, Japan. Electronic address: s0911688@u.tsukuba.ac.jp.
    • Life Sci. 2014 Nov 24; 118 (2): 347-56.

    AimsEndothelin (ET)-1 is the best known potent vasoconstrictor and has been implicated in pathogenesis of sepsis-associated acute kidney injury (AKI) in human or lipopolysaccharide (LPS)-induced AKI in animal models. We have previously shown that ET-1 is highly up-regulated in renal tissues and in plasma after LPS administration. Here, we investigated whether landiolol hydrochloride, an ultra-short-acting beta-blocker, can play an important role in ameliorating levels of LPS-induced up-regulation of renal HIF-1α-ET-1 system and inflammatory cytokines in a rat model of endotoxemia.Main MethodsMale Wistar rats at 8 weeks of age were either administered with: a) lipopolysaccharide (LPS) only for three hours (3 h) or b) LPS, followed by continuous administration of landiolol for 3 h; c) third group was only treated with vehicle.Key FindingsAt 3 h after LPS administration there was: a) minimal injury in kidney tissues; b) circulatory levels of creatinine, blood urea nitrogen and NGAL increased and c) expression of inflammatory cytokines, such as TNF-α, IL-6 and iNOS increased at the level of both circulatory and renal tissues. In addition, LPS significantly induced renal expression of ET-1 and HIF-1α compared to control. Finally, treatment of LPS-administered rats with landiolol for 3 h normalized elevated serum markers of renal injury and up-regulated levels of renal HIF-1α-ET-1 system with normalization of TNF-α.SignificanceTaken together, these data led us to conclude that landiolol ameliorates the up-regulation of HIF-1α-ET-1 system in minimally morphologically-injured kidney and normalizes biomarkers of renal injury in early hours of endotoxemia of a rat model.Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

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