Renoprotective effect of yohimbine on ischaemia/reperfusion-induced acute kidney injury through α2C-adrenoceptors in rats

  • Eur J Pharmacol. 2016 Jun 15;781:36-44. doi: 10.1016/j.ejphar.2016.03.059.
Takaomi Shimokawa  1 ,  Hidenobu Tsutsui  2 ,  Takeshi Miura  3 ,  Toru Nishinaka  4 ,  Tomoyuki Terada  4 ,  Masashi Takama  5 ,  Shuhei Yoshida  2 ,  Takao Tanba  2 ,  Ayumi Tojo  2 ,  Masayo Yamagata  2 ,  Tokihito Yukimura  2
Affiliations
  • 1. Laboratory of Clinical Pharmacology, Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nshikiori-kita, Tondabayashi, Osaka 584-8540, Japan. Electronic address: [email protected].
  • 2. Laboratory of Clinical Pharmacology, Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nshikiori-kita, Tondabayashi, Osaka 584-8540, Japan.
  • 3. Pharmaceutical Education Support Center, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, 9-11-68 Koshien, Nishinomiya, Osaka 663-8179, Japan.
  • 4. Laboratory of Biochemistry, Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nshikiori-kita, Tondabayashi, Osaka 584-8540, Japan.
  • 5. Laboratory of Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nshikiori-kita, Tondabayashi, Osaka 584-8540, Japan.
PMID: 27041645 DOI: 10.1016/j.ejphar.2016.03.059
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.

Keywords
Acute kidney injury; Ischaemia/reperfusion; Norepinephrine; Yohimbine.
Products