Endothelial dysfunction in the mesenteric artery and disturbed nonadrenergic noncholinergic relaxation of the ileum due to intestinal ischemia-reperfusion can be prevented by sildenafil.
The aim of the present study was to evaluate the effects of sildenafil on endothelium-dependent mesenteric artery vasorelaxation and nonadrenergic noncholinergic (NANC) ileal responses in an experimental rat intestinal ischemia-reperfusion (I/R) model. The superior mesenteric artery was occluded for 45 min of ischemia and then the clamp was removed for 60 min of reperfusion. Sildenafil (1 mg/kg, i.v.) or saline was administered prior to surgery in the I/R and sham-operated groups. Acetylcholine-induced relaxation of the mesenteric arteries, which were precontracted via submaximal phenylephrine, decreased markedly after I/R. Sildenafil pretreatment reversed the acetylcholine-induced relaxation. In the ileum, NANC responses were significantly attenuated following I/R, which were increased by sildenafil pretreatment. These results indicate that pretreatment with sildenafil prevented both endothelial dysfunction in the mesenteric artery and impairment of ileal NANC responses in a rat intestinal I/R model.
Soydan
Guray
G
Department of Pharmacology, Hacettepe University, Ankara, Turkey.
Cekiç
Edip Guvenç
EG
Tuncer
Meral
M
D000109:Acetylcholine; D000818:Animals; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D007082:Ileum / Q000187:drug effects / Q000503:physiopathology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects / Q000378:metabolism; D010656:Phenylephrine; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D010656:Phenylephrine; D000068677:Sildenafil Citrate; D000109:Acetylcholine