Cholinergic Agonists Attenuate Renal Ischemia-reperfusion Injury in Rats

Overview

Journal Kidney Int

Publisher Elsevier

Specialty Nephrology

Date 2008 Apr 11

PMID 18401335

Citations 71

Authors

M M Yeboah

X Xue

B Duan

M Ochani

K J Tracey

M Susin

C N Metz

Affiliations

Soon will be listed here.

Abstract

Inflammation plays a significant role in the pathophysiology of renal ischemia-reperfusion injury. Local inflammation is modulated by the brain via the vagus nerve and nicotinic acetylcholine receptors such that electrical or pharmacologic stimulation of this cholinergic anti-inflammatory pathway results in suppression of proinflammatory cytokine production. We examined the effects of cholinergic stimulation using agonists, nicotine or GTS-21, given before or after bilateral renal ischemia-reperfusion injury in rats. Pretreatment of rats with either agonist significantly attenuated renal dysfunction and tubular necrosis induced by renal ischemia. Similarly, tumor necrosis factor-alpha protein expression and leukocyte infiltration of the kidney were markedly reduced following treatment with cholinergic agonists. We found functional nicotinic acetylcholine receptors were present on rat proximal tubule epithelial cells. Cholinergic stimulation significantly decreased tubular necrosis in vagotomized rats after injury, implying an intact vagus nerve is not required for this renoprotective effect.

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