Open AccessDexmedetomidine preconditioning ameliorates kidney ischemia‐reperfusion injury
Author(s) -
Lempiäinen Juha,
Finckenberg Piet,
Mervaala Elina E.,
Storvik Markus,
Kaivola Juha,
Lindstedt Ken,
Levijoki Jouko,
Mervaala Eero M.
Publication year - 2014
Publication title -
pharmacology research and perspectives
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.975
H-Index - 27
ISSN - 2052-1707
DOI - 10.1002/prp2.45
Subject(s) - kidney , pharmacology , medicine , renal ischemia , acute kidney injury , reperfusion injury , endocrinology , dexmedetomidine , ischemia , sedation
Kidney ischemia‐reperfusion (I/R) injury is a common cause of acute kidney injury. We tested whether dexmedetomidine (Dex), an alpha2 adrenoceptor ( α 2‐AR) agonist, protects against kidney I/R injury. Sprague–Dawley rats were divided into four groups: (1) Sham‐operated group; (2) I/R group (40 min ischemia followed by 24 h reperfusion); (3) I/R group + Dex (1 μ g/kg i.v. 60 min before the surgery), (4) I/R group + Dex (10 μ g/kg). The effects of Dex postconditiong (Dex 1 or 10 μ g/kg i.v. after reperfusion) as well as the effects of peripheral α 2‐AR agonism with fadolmidine were also examined. Hemodynamic effects were monitored, renal function measured, and acute tubular damage along with monocyte/macrophage infiltration scored. Kidney protein kinase B, toll like receptor 4, light chain 3B, p38 mitogen‐activated protein kinase (p38 MAPK), sirtuin 1, adenosine monophosphate kinase (AMPK), and endothelial nitric oxide synthase (eNOS) expressions were measured, and kidney transciptome profiles analyzed. Dex preconditioning, but not postconditioning, attenuated I/R injury‐induced renal dysfunction, acute tubular necrosis and inflammatory response. Neither pre‐ nor postconditioning with fadolmidine protected kidneys. Dex decreased blood pressure more than fadolmidine, ameliorated I/R‐induced impairment of autophagy and increased renal p38 and eNOS expressions. Dex downregulated 245 and upregulated 61 genes representing 17 enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, in particular, integrin pathway and CD44. Ingenuity analysis revealed inhibition of Rac and nuclear factor (erythroid‐derived 2)‐like 2 pathways, whereas aryl hydrocarbon receptor (AHR) pathway was activated. Dex preconditioning ameliorates kidney I/R injury and inflammatory response, at least in part, through p38‐CD44‐pathway and possibly also through ischemic preconditioning.