Moxonidine prevents ischemia/reperfusion-induced renal injury in rats.
Enhancement of renal sympathetic nerve activity during renal ischemia and its consequent effect on norepinephrine overflow from nerve endings after reperfusion play important roles in the development of ischemic acute kidney injury. In the present study, we evaluated whether moxonidine, an alpha(2)-adrenaline/I(1)-imidazoline receptor agonist which is known to elicit sympathoinhibitory action, would prevent the post-ischemic renal injury. 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. Intravenous (i.v.) injection of moxonidine at a dose of 360 nmol/kg to ischemic acute kidney injury rats suppressed the enhanced renal sympathetic nerve activity during the ischemic period, to a degree similar to findings with intracerebroventricular (i.c.v.) injection of moxonidine at a dose of 36 nmol/kg. On the other hand, suppressive effects of the i.v. treatment on renal venous norepinephrine overflow, renal dysfunction and tissue injury in the post-ischemic kidney were significantly greater than those elicited by the i.c.v. treatment. These results suggest that renoprotective effects of moxonidine on ischemic acute kidney injury probably result from its suppressive action on the ischemia-enhanced renal sympathetic nerve activity followed by norepinephrine spillover from the nerve endings of the post-ischemic kidney.
Tsutsui
Hidenobu
H
Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan.
Sugiura
Takahiro
T
Hayashi
Kentaro
K
Ohkita
Mamoru
M
Takaoka
Masanori
M
Yukimura
Tokihito
T
Matsumura
Yasuo
Y
D000322:Adrenergic Agonists / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D007093:Imidazoles / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D048288:Imidazolines / Q000737:chemistry; D007275:Injections, Intravenous; D007511:Ischemia / Q000503:physiopathology; D007668:Kidney / Q000294:innervation* / Q000503:physiopathology*; D007674:Kidney Diseases / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D009638:Norepinephrine / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications* / Q000473:pathology / Q000503:physiopathology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014680:Veins / Q000187:drug effects / Q000378:metabolism
D000322:Adrenergic Agonists; D007093:Imidazoles; D048288:Imidazolines; C043482:moxonidine; D009638:Norepinephrine