The effects of sildenafil on the functional and structural changes of ileum induced by intestinal ischemia-reperfusion in rats.
There is evidence demonstrating the protective effect of cGMP-specific phosphodiesterase type 5 (PDE5) inhibitors against ischemic injury in certain tissues. In this study, sildenafil, a potent inhibitor of PDE5, was tested for its beneficial effects in the prevention of disrupted ileal contractility and damage to tissue caused by intestinal ischemia-reperfusion in rats. Male Sprague-Dawley rats were divided into four groups: sham-operated; sham-operated with sildenafil pretreatment; ischemia-reperfusion with vehicle pretreatment; and ischemia-reperfusion with sildenafil pretreatment. The superior mesenteric artery was occluded for 45 min to induce ischemia. The clamp was then removed for a 60 min period of reperfusion. Sildenafil (1 mg/kg, i.v.) or saline was administered prior to the surgical procedure in the ischemia-reperfusion and sham-operated groups. Isometric contractions of the ileal segments in response to acetylcholine or electrical field stimulation (120 V, 2 ms pulse for 5 s, 1-20 Hz) were recorded. Additionally, levels of thiobarbituric acid reactive substances and myeloperoxidase activity were measured in addition to a histopathological examination of the ileal tissue. The contractions induced by both acetylcholine and electrical field stimulations were markedly inhibited after ischemia-reperfusion. Sildenafil pretreatment (1 mg/kg, i.v.) abolished the inhibition of responses to acetylcholine. The increased levels of thiobarbituric acid reactive substances and myeloperoxidase activity caused by ischemia-reperfusion were reversed to control levels with sildenafil pretreatment. Intestinal ischemia-reperfusion caused severe ischemic injury in rat ileum, which was prevented by sildenafil. These results suggest that sildenafil pretreatment has a protective effect against ileal dysfunction and damage induced by intestinal ischemia-reperfusion in the rat.
Soydan
Güray
G
Department of Pharmacology, Hacettepe University, Ankara 06100, Turkey.
Sökmensüer
Cenk
C
Kilinç
Kamer
K
Tuncer
Meral
M
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D007082:Ileum / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D007413:Intestinal Mucosa / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D007537:Isometric Contraction; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008839:Microelectrodes; D009119:Muscle Contraction / Q000187:drug effects*; D009504:Neutrophils / Q000378:metabolism; D010477:Perfusion; D009195:Peroxidase / Q000032:analysis; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology*; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014665:Vasodilator Agents / Q000494:pharmacology
D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D017392:Thiobarbituric Acid Reactive Substances; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate; D009195:Peroxidase; D000109:Acetylcholine