Cholinergic agonists attenuate renal ischemia-reperfusion injury in rats.
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.
Yeboah
M M
MM
Laboratory of Medicinal Biochemistry, The Feinstein Institute for Medical Research, North Shore-LIJ Health System, Manhasset, New York 11030, USA.
Xue
X
X
Duan
B
B
Ochani
M
M
Tracey
K J
KJ
Susin
M
M
Metz
C N
CN
D000818:Animals; D002634:Chemotaxis, Leukocyte; D018679:Cholinergic Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D007249:Inflammation / Q000473:pathology; D007674:Kidney Diseases / Q000188:drug therapy / Q000473:pathology*; D008297:Male; D009336:Necrosis / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014630:Vagus Nerve
D018679:Cholinergic Agonists; D014409:Tumor Necrosis Factor-alpha