Cholinergic agonists attenuate renal ischemia–reperfusion injury in rats

• Published in: Kidney international Vol. 74; no. 1; pp. 62 - 69
• Main Authors: Yeboah, M.M., Xue, X., Duan, B., Ochani, M., Tracey, K.J., Susin, M., Metz, C.N.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.07.2008; Nature Publishing; Elsevier Limited
• Subjects: Animals; Biological and medical sciences; Chemotaxis, Leukocyte; Cholinergic Agonists - pharmacology; Cholinergic Agonists - therapeutic use; GTS-21; inflammation; Inflammation - pathology; Kidney Diseases - drug therapy; Kidney Diseases - pathology; Male; Medical sciences; Necrosis - prevention & control; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; nicotine; Rats; Rats, Sprague-Dawley; renal ischemia–reperfusion injury; Renovascular diseases; Reperfusion Injury - drug therapy; Reperfusion Injury - pathology; TNF; tubular epithelial cells; Tumor Necrosis Factor-alpha - analysis; Vagus Nerve; GTS-21; nicotine; inflammation; tubular epithelial cells; TNF; renal ischemia–reperfusion injury; Agonist; Nephrology; Rat; Cardiovascular disease; Kidney; Urology; Alkaloid; Kidney disease; Urinary system disease; Cytokine; Rodentia; Inflammation; Vertebrata; Renal tubule; Mammalia; Urinary system; Tumor necrosis factor; Animal; renal ischemia-reperfusion injury; Epithelial cell; Renal ischemia reperfusion injury; Nicotine
• ISSN: 0085-2538; 1523-1755
• DOI: 10.1038/ki.2008.94

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-α 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.