The Journal of surgical research · 2020
Tachykinin Antagonists Reverse Ischemia/Reperfusion Gastrointestinal Motility Impairment in Rats.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Umer Artur, Ługowska-Umer Hanna, Schönborn-Kellenberger Oliver, Korolkiewicz Paweł K, Sein-Anand Łukasz, Kuziemski Krzysztof, Korolkiewicz Roman P
Аннотация
BACKGROUND: Supraceliac aortic clamping and unclamping produces ischemia-reperfusion (I/R) injury of the splanchnic organs. The protective effects of tachykinin receptor antagonists, SR140333 (NK1 receptor), SR48968 (NK2 receptor), and SB222200 (NK3 receptor), against I/R-induced inhibition of intestinal motility were tested in rats.
MATERIAL AND METHODS: The intestinal transit of Evans blue was measured in untreated rats and animals subjected to skin incision, I/R (1 h superior mesenteric artery occlusion followed by 24 h reperfusion) or sham operation. Surgical procedures were conducted under diethyl ether anesthesia.
RESULTS: The gastrointestinal transit has not been markedly affected in rats, which were anesthetized or subjected to skin incision in comparison with untreated animals. In contrast, a sham operation and I/R have significantly reduced the intestinal motility. Pretreatment with NK1-3 blockers (SR140333 [3-30 μg/kg]; SR48968 [3-100 μg/kg]; and SB222200 [10-100 μg/kg]) reversed dose dependently the effects of I/R to the level observed after sham operation only. A combination of NK1+NK2+NK3 inhibitors exerted an additive effect compared with NK1 and NK2 antagonists used as single agents. Similarly, combined NK1+NK2 were more effective than NK2 alone. Sham operation and I/R have shifted the in vitro carbachol concentration-response curves to the right in comparison with untreated animals, a phenomenon partially reversed by NK1-NK3 pretreatment.
CONCLUSIONS: Single-agent and combined treatment with NK1-3 antagonists markedly attenuated the gastrointestinal dysmotility evoked by I/R injury. The pretreatment with NK3 blocker proved to be the most active in this experimental setting.
MATERIAL AND METHODS: The intestinal transit of Evans blue was measured in untreated rats and animals subjected to skin incision, I/R (1 h superior mesenteric artery occlusion followed by 24 h reperfusion) or sham operation. Surgical procedures were conducted under diethyl ether anesthesia.
RESULTS: The gastrointestinal transit has not been markedly affected in rats, which were anesthetized or subjected to skin incision in comparison with untreated animals. In contrast, a sham operation and I/R have significantly reduced the intestinal motility. Pretreatment with NK1-3 blockers (SR140333 [3-30 μg/kg]; SR48968 [3-100 μg/kg]; and SB222200 [10-100 μg/kg]) reversed dose dependently the effects of I/R to the level observed after sham operation only. A combination of NK1+NK2+NK3 inhibitors exerted an additive effect compared with NK1 and NK2 antagonists used as single agents. Similarly, combined NK1+NK2 were more effective than NK2 alone. Sham operation and I/R have shifted the in vitro carbachol concentration-response curves to the right in comparison with untreated animals, a phenomenon partially reversed by NK1-NK3 pretreatment.
CONCLUSIONS: Single-agent and combined treatment with NK1-3 antagonists markedly attenuated the gastrointestinal dysmotility evoked by I/R injury. The pretreatment with NK3 blocker proved to be the most active in this experimental setting.