Involvement of corticotropin-releasing factor and corticotropin-releasing factor 2 receptors in pathogenesis of ischemia/reperfusion-induced enteritis in rats

We herein investigated,using a corticotropin-releasing factor (crf) agonist and antagonists,whether crf plays a role in the pathogenesis of ischemia/reperfusion-induced small intestinal lesions in rats. under pentobarbital anesthesia,the superior mesenteric artery was clamped (ischemia) for 75 min,followed by reperfusion with removal of the clamp. after a 24-h reperfusion,the area of hemorrhagic lesions that developed in the small intestine was measured. urocortin i (crf receptor 1/2 agonist),astressin (crf receptor 1/2 antagonist),nbi27914 (crf receptor 1 antagonist),or astressin 2b (crf receptor 2 antagonist) was administered i.v. twice: 5 min before ischemia and 6 hours after reperfusion. ischemia/reperfusion caused hemorrhagic lesions in the small intestine in ampicillin-and aminoguanidine-inhibitable manners,accompanied by enterobacterial invasion and the up-regulation of inducible nitric oxide synthase expression and myeloperoxidase activity. the severity of ischemia/reperfusion-induced lesions was significantly reduced by astressin and astressin 2b,but not by nbi27914,with the suppression of bacterial invasion,myeloperoxidase activity,and inducible nitric oxide synthase expression. in contrast,urocortin i markedly aggravated these lesions,and this response was completely abrogated by the co-administration of astressin 2b,but not nbi27914. the gene expression of crf,crf receptor 1,and crf receptor 2 was observed in the small intestine,and remained unchanged following ischemia/reperfusion. these results suggest that ischemia/reperfusion caused hemorrhagic lesions in the small intestine,the pathogenesis of which involved enterobacteria and inducible nitric oxide synthase/nitric oxide. these lesions were aggravated by urocortin i in an astressin 2b-inhibitable manner,but suppressed by astressin in a crf receptor 2-dependent manner. endogenous crf may be involved in the pathogenesis of ischemia/reperfusion-induced enteritis,possibly via the activation of peripheral crf receptor 2. © 2016,polish physiological society. all rights reserved.