Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Involvement of corticotropin-releasing factor and corticotropin-releasing factor 2 receptors in pathogenesis of ischemia/reperfusion-induced enteritis in rats. 2801 50


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