title: Renoprotective effect of yohimbine on ischaemia/reperfusion-induced acute kidney injury through α2C-adrenoceptors in rats.
abstract: Excitation of renal sympathetic nervous activity and the resulting increased levels of renal venous norepinephrine play important roles in renal ischaemia/reperfusion injury in rats. This study examined the effects of yohimbine, a non-selective α2-adrenoceptor antagonist, on renal venous norepinephrine levels and kidney function in acute kidney injury. Acute ischaemia/reperfusion-induced kidney injury was induced in rats by clamping the left renal artery and vein for 45min, followed by reperfusion, 2 weeks after a contralateral nephrectomy. Intravenous injection of yohimbine (0.1mg/kg) 5min prior to ischaemia significantly attenuated kidney injury and decreased the renal venous norepinephrine levels, as compared with vehicle-treated rats. To investigate the involvement of α2-adrenoceptor subtypes, we pre-treated with JP-1302, a selective α2C-adrenoceptor antagonist (1mg/kg). This suppressed renal venous norepinephrine levels and tumour necrosis factor-α and monocyte chemoattractant protein-1 mRNA levels after reperfusion and improved kidney function. Pre-treatment with BRL44408, a selective α2A-adrenoceptor antagonist (1mg/kg), or imiloxan, a selective α2B-adrenoceptor antagonist (1mg/kg) had no effect on renal function or tissue injury. These results suggest that yohimbine prevented ischaemia/reperfusion-induced kidney injury by inhibiting α2C-adrenoceptors and suppressing pro-inflammatory cytokine expression.
authors.affiliation: Laboratory of Clinical Pharmacology, Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nshikiori-kita, Tondabayashi, Osaka 584-8540, Japan. Electronic address: simokataka@osaka-ohtani.ac.jp.
authors.forename: Takaomi
authors.initials: T
authors.lastname: Shimokawa
authors.affiliation: Laboratory of Clinical Pharmacology, Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nshikiori-kita, Tondabayashi, Osaka 584-8540, Japan.
authors.forename: Hidenobu
authors.initials: H
authors.lastname: Tsutsui
authors.affiliation: Pharmaceutical Education Support Center, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, 9-11-68 Koshien, Nishinomiya, Osaka 663-8179, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Miura
authors.affiliation: Laboratory of Biochemistry, Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nshikiori-kita, Tondabayashi, Osaka 584-8540, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Nishinaka
authors.affiliation: Laboratory of Biochemistry, Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nshikiori-kita, Tondabayashi, Osaka 584-8540, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Terada
authors.affiliation: Laboratory of Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nshikiori-kita, Tondabayashi, Osaka 584-8540, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Takama
authors.affiliation: Laboratory of Clinical Pharmacology, Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nshikiori-kita, Tondabayashi, Osaka 584-8540, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Yoshida
authors.affiliation: Laboratory of Clinical Pharmacology, Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nshikiori-kita, Tondabayashi, Osaka 584-8540, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Tanba
authors.affiliation: Laboratory of Clinical Pharmacology, Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nshikiori-kita, Tondabayashi, Osaka 584-8540, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Tojo
authors.affiliation: Laboratory of Clinical Pharmacology, Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nshikiori-kita, Tondabayashi, Osaka 584-8540, Japan.
authors.forename: Masayo
authors.initials: M
authors.lastname: Yamagata
authors.affiliation: Laboratory of Clinical Pharmacology, Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nshikiori-kita, Tondabayashi, Osaka 584-8540, Japan.
authors.forename: Tokihito
authors.initials: T
authors.lastname: Yukimura
mesh_terms: D000166:Acridines / Q000494:pharmacology; D058186:Acute Kidney Injury / Q000097:blood / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D015427:Reperfusion Injury / Q000150:complications*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015016:Yohimbine / Q000494:pharmacology*
chemical_list: D000166:Acridines; D058669:Adrenergic alpha-2 Receptor Antagonists; D018932:Chemokine CCL2; C518829:JP-1302; D010879:Piperazines; D018341:Receptors, Adrenergic, alpha-2; D014409:Tumor Necrosis Factor-alpha; D015016:Yohimbine; D009638:Norepinephrine
keywords: Acute kidney injury; Ischaemia/reperfusion; Norepinephrine; Yohimbine