Preventive mechanisms of agmatine against ischemic acute kidney injury in rats.
The excitation of renal sympathetic nervous system plays an important role in the development of ischemic acute kidney injury in rats. Recently, we found that agmatine, an adrenaline alpha(2)/imidazoline I(1)-receptor agonist, has preventive effects on ischemic acute kidney injury by suppressing the enhanced renal sympathetic nerve activity during renal ischemia and by decreasing the renal venous norepinephrine overflow after reperfusion. In the present study, we investigated preventive mechanisms of agmatine against ischemic acute kidney injury in rats. Ischemic acute kidney injury was induced by clamping the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after the contralateral nephrectomy. Pretreatment with efaroxan (30 mumol/kg, i.v.), an alpha(2)/I(1)-receptor antagonist, abolished the suppressive effects of agmatine on the enhanced renal sympathetic nerve activity during renal ischemia and on the elevated norepinephrine overflow after reperfusion, and eliminated the preventing effects of agmatine on the ischemia/reperfusion-induced renal dysfunction and histological damage. On the other hand, pretreatment with yohimbine (6 mumol/kg, i.v.), an alpha(2)-receptor antagonist, eliminated the preventing effects of agmatine on the ischemia/reperfusion-induced renal injury and norepinephrine overflow, without affecting the lowering effect of agmatine on renal sympathetic nerve activity. These results indicate that agmatine prevents the ischemic renal injury by sympathoinhibitory effect probably via I(1) receptors in central nervous system and by suppressing the norepinephrine overflow through alpha(2) or I(1) receptors on sympathetic nerve endings.
Sugiura
Takahiro
T
Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan.
Kobuchi
Shuhei
S
Tsutsui
Hidenobu
H
Takaoka
Masanori
M
Fujii
Toshihide
T
Hayashi
Kentaro
K
Matsumura
Yasuo
Y
D058669:Adrenergic alpha-2 Receptor Antagonists; D000376:Agmatine / Q000494:pharmacology*; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D054755:Imidazoline Receptors / Q000037:antagonists & inhibitors; D007674:Kidney Diseases / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D009638:Norepinephrine / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism; D014680:Veins / Q000187:drug effects / Q000378:metabolism; D015016:Yohimbine / Q000494:pharmacology
D058669:Adrenergic alpha-2 Receptor Antagonists; D001572:Benzofurans; D007093:Imidazoles; D054755:Imidazoline Receptors; C410887:imidazoline I1 receptors; D015016:Yohimbine; D000376:Agmatine; C062597:efaroxan; D009638:Norepinephrine