title: Protective effect of agmatine on ischemia/reperfusion-induced renal injury in rats.
abstract: Enhanced renal sympathetic nerve activity (RSNA) during ischemic period and the renal venous norepinephrine (NE) overflow after reperfusion play important roles in the development of ischemic/reperfusion (I/R)-induced acute renal failure (ARF) in rats. This study evaluated whether agmatine, which is known to reduce sympathetic nerve activity and NE overflow by electrical stimulation, would prevent the I/R-induced renal dysfunction. Ischemic ARF was induced by clamping the left renal artery and vein for 45 minutes followed by reperfusion 2 weeks after the contralateral nephrectomy. Intravenous (IV) injection of agmatine (100 and 300 micromol/kg) to ischemic ARF rats dose-dependently suppressed the enhanced RSNA and attenuated the I/R-induced renal dysfunction and histological damage. Intracerebroventricular (ICV) injection of agmatine (600 nmol/kg) to ischemic ARF rats suppressed the enhanced RSNA during the ischemic period and attenuated the I/R-induced renal injury. Furthermore, both IV and ICV injection of agmatine significantly suppressed the renal venous NE overflow after the reperfusion. These results indicate that agmatine prevents the development of I/R-induced renal injury, and the effect is accompanied by suppression of the enhanced RSNA during ischemic period and NE overflow from renal sympathetic nerve endings.
authors: Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan.
authors: Takahiro
authors: T
authors: Sugiura
authors: Hidenobu
authors: H
authors: Tsutsui
authors: Masanori
authors: M
authors: Takaoka
authors: Shuhei
authors: S
authors: Kobuchi
authors: Kentaro
authors: K
authors: Hayashi
authors: Toshihide
authors: T
authors: Fujii
authors: Yasuo
authors: Y
authors: Matsumura
mesh_terms: D058186:Acute Kidney Injury / Q000517:prevention & control*; D000376:Agmatine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications*; D013564:Sympathetic Nervous System / Q000187:drug effects*
chemical_list: D000376:Agmatine; D009638:Norepinephrine