Protective effect of moxonidine on ischemiaireperfusion-induced acute kidney injury through α2/imidazoline I1 receptor

被引:10
作者
Tsutsui, Hidenobu [1 ,2 ]
Sugiura, Takahiro [1 ]
Hayashi, Kentaro [1 ]
Yukimura, Tokihito [2 ]
Ohkita, Mamoru [1 ]
Takaoka, Masanori [1 ]
Matsumura, Yasuo [1 ]
机构
[1] Osaka Univ Pharmaceut Sci, Lab Pathol & Mol Pharmacol, 4-20-1 Nasahara, Takatsuki, Osaka 5691094, Japan
[2] Osaka Ohtani Univ, Fac Pharm, Lab Clin Pharmacol, Tondabayashi, Osaka 5848540, Japan
关键词
Moxonidine; Renal sympathetic nerve activity; Norepinephrine; Ischemia/reperfusion; Acute kidney injury; SYMPATHETIC-NERVOUS-SYSTEM; INDUCED RENAL INJURY; NOREPINEPHRINE OVERFLOW; NORADRENALINE RELEASE; ISCHEMIA/REPERFUSION; PROPRANOLOL; PATHOGENESIS; MECHANISMS; CLONIDINE; ISCHEMIA;
D O I
10.1016/j.ejphar.2013.08.036
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 alpha 2/imidazoline I-1-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, iv,) against ischemic acute kidney injury, we investigated the effect of intravenous (ix.) and intracerebroventricular (i.c.v) injection of efaroxan, an alpha 2/I-1 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 iv. (360 nmol/kg) or i.c.v. (36 nmol/kg) of efaroxan. Furthermore, iv. injection of efaroxan eliminated the preventive effect of moxonidine on ischemiaffeperfusion-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 alpha 2/I-1 receptors in central nervous system and by suppressing the norepinephrine overflow through alpha 2/I-1 receptors on sympathetic nerve endings. 2013 Elsevier B.V. All rights reserved.
引用
收藏
页码:173 / 180
页数:8
相关论文
共 27 条
[1]   NERVOUS DISORDERS OF RENAL-FUNCTION [J].
BAINES, AD .
CLINICAL BIOCHEMISTRY, 1983, 16 (02) :134-140
[2]  
BOHMANN C, 1994, N-S ARCH PHARMACOL, V349, P118
[3]   Role of endothelium-related mechanisms in the pathophysiology of renal ischemia/reperfusion in normal rabbits [J].
Caramelo, C ;
Espinosa, G ;
Manzarbeitia, F ;
Cernadas, MR ;
Tejerizo, GP ;
Tan, D ;
Mosquera, JR ;
Digiuni, E ;
Monton, M ;
Millas, I ;
Hernando, L ;
Casado, S ;
LopezFarre, A .
CIRCULATION RESEARCH, 1996, 79 (05) :1031-1038
[4]   EFFECTS OF PROPRANOLOL ON POST-ISCHEMIC ACUTE-RENAL-FAILURE [J].
CHEVALIER, RL ;
FINN, WF .
NEPHRON, 1980, 25 (02) :77-81
[5]   α2B-Adrenergic receptors activate MAPK and modulate proliferation of primary cultured proximal tubule cells [J].
Cussac, D ;
Schaak, S ;
Gales, C ;
Flordellis, C ;
Denis, C ;
Paris, H .
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 2002, 282 (05) :F943-F952
[6]   The nature of renal cell injury [J].
Edelstein, CL ;
Ling, H ;
Schrier, RW .
KIDNEY INTERNATIONAL, 1997, 51 (05) :1341-1351
[7]   'Seeing through a glass darkly': casting light on imidazoline 'I' sites [J].
Eglen, RM ;
Hudson, AL ;
Kendall, DA ;
Nutt, DJ ;
Morgan, NG ;
Wilson, VG ;
Dillon, MP .
TRENDS IN PHARMACOLOGICAL SCIENCES, 1998, 19 (09) :381-390
[8]  
ERNSBERGER P, 1990, J PHARMACOL EXP THER, V253, P408
[9]  
ERNSBERGER P, 1993, J PHARMACOL EXP THER, V264, P172
[10]   The role of renal sympathetic nervous system in the pathogenesis of ischemic acute renal failure [J].
Fujii, T ;
Kurata, H ;
Takaoka, M ;
Muraoka, T ;
Fujisawa, Y ;
Shokoji, T ;
Nishiyama, A ;
Abe, Y ;
Matsumura, Y .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2003, 481 (2-3) :241-248