Evidence for the involvement of 5-HT2A receptors in mild mesenteric ischemia/reperfusion dysfunctions in mice

In this study, the involvement of 5-HT2A receptors on mesenteric ischemia-reperfusion injury was examined in mice. Intestinal ischemia produced by 45 min occlusion of superior mesenteric artery was followed by 24 h reperfusion (I/R). The 5-HT2A selective antagonist, ketanserin (0.5 mg kg−1) or the 5-HT2A agonist DOI (0.25 mg kg−1) was intravenously administered before ischemia and 8 h after the beginning of reperfusion. The effects were compared with those obtained in sham operated animals (S). Ketanserin prevented the upper gastrointestinal transit delay induced by I/R (P < 0.01), protected intestine from leukocyte recruitment as indicated by jejunal myeloperoxidase activity (P < 0.05) and reverted Evans Blue extravasation elicited by I/R in lung, colon and jejunum (P < 0.05). On the other hand, 5-HT2A activation by DOI mimicked the effects of I/R in S mice prolonging small intestine transit (P < 0.05) and enhancing neutrophil accumulation in jejunal tissues (P < 0.05). Furthermore, the reduction of ADP-induced platelet aggregation in plasma of I/R mice was prevented by ketanserin treatment. All together, these findings support the critical involvement of 5-HT2A receptor subtype in mediating the damage induced by mesenteric I/R in mice.