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.