title: Protective effect of moxonidine on ischemia/reperfusion-induced acute kidney injury through α2/imidazoline I1 receptor.
abstract: Enhancement of renal sympathetic nerve activity during renal ischemia and norepinephrine overflow from the kidney after reperfusion play important roles in the development of ischemic acute kidney injury. Recently, we have found that moxonidine, an α2/imidazoline Ι1-receptor agonist, has preventive effects on ischemic acute kidney injury by suppressing the excitation of renal sympathetic nervous system after reperfusion. In the present study, to clarify the renoprotective mechanisms of moxonidine (360 nmol/kg, i.v.) against ischemic acute kidney injury, we investigated the effect of intravenous (i.v.) and intracerebroventricular (i.c.v.) injection of efaroxan, an α2/Ι1 receptor antagonist, on the moxonidine-exhibited actions. Ischemic acute kidney injury was induced by clamping the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. The suppressive effect of moxonidine on enhanced renal sympathetic nerve activity during renal ischemia was not observed in the rat treated with either i.v. (360 nmol/kg) or i.c.v. (36 nmol/kg) of efaroxan. Furthermore, i.v. injection of efaroxan eliminated the preventive effect of moxonidine on ischemia/reperfusion-induced kidney injury and norepinephrine overflow, and i.c.v. injection of efaroxan did not completely inhibit the moxonidine's effects. These results indicate that moxonidine prevents the ischemic kidney injury by sympathoinhibitory effect probably via α2/Ι1 receptors in central nervous system and by suppressing the norepinephrine overflow through α2/Ι1 receptors on sympathetic nerve endings.
authors.affiliation: Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan; Laboratory of Clinical Pharmacology, Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nishikiori-kita, Tondabayashi, Osaka 584-8540, Japan.
authors.forename: Hidenobu
authors.initials: H
authors.lastname: Tsutsui
authors.forename: Takahiro
authors.initials: T
authors.lastname: Sugiura
authors.forename: Kentaro
authors.initials: K
authors.lastname: Hayashi
authors.forename: Tokihito
authors.initials: T
authors.lastname: Yukimura
authors.forename: Mamoru
authors.initials: M
authors.lastname: Ohkita
authors.forename: Masanori
authors.initials: M
authors.lastname: Takaoka
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Matsumura
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology; D019610:Cytoprotection; D007093:Imidazoles / Q000494:pharmacology*; D054755:Imidazoline Receptors / Q000378:metabolism*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009638:Norepinephrine / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology; D014680:Veins / Q000187:drug effects / Q000378:metabolism
chemical_list: D001572:Benzofurans; D007093:Imidazoles; D054755:Imidazoline Receptors; C410887:imidazoline I1 receptors; C043482:moxonidine; C062597:efaroxan; D009638:Norepinephrine
keywords: Acute kidney injury; Ischemia/reperfusion; Moxonidine; Norepinephrine; Renal sympathetic nerve activity