Early inflammation induced by a subchronic treatment with ILs causes changes in mucosal ionic transport parameters, a reduction in the direct contractile response, and an alteration in the neurotransmission (by an enhancing cholinergic component) that may affect the physiological pattern of colonic motility and the sensory reflex.

No abstract

1. Inflammatory bowel disease (IBD) is a condition that involves proinflammatory cytokines such as interleukins 1beta and 6 (ILs). In this disease, it has been shown that an abnormal microcirculatory system is implicated. 2. Therefore, the effects of in vivo treatment for three days with interleukins 1beta and 6 were investigated on rat isolated mesenteric vascular bed (MVB). 3. A significant concentration-dependent increase in vascular response to noradrenaline (NA) was found, with a significant difference in Emax between control (93.01 +/- 16.78 mmHg) and treated preparations (137.91 +/- 5.20 mmHg). Endothelin-1(ET-1) induced a significantly greater increase of perfusion pressure in treated rats in comparison with control rats at the highest concentration used (0.1 microm). 4. The concentration-dependent decrease of perfusion pressure induced by acetylcholine (ACh) in MVB precontracted with NA was significantly reduced in specimens from treated rats in comparison with control rats, with a significant difference in Emax between control and treated preparations. 5. Perivascular nerve stimulation (PNS) evoked contractions with no difference between treatments. Similarly, no difference in relaxant effect was found after PNS in specimens precontracted with NA, in the presence of guanethidine. 6. These findings indicate that the precocious inflammation acts only at postsynaptic level, facilitating vascular contraction. These data seem to support the hypothesis that vascular dysfunction caused by overproduction of ILs may contribute, among other immunological factors, to vasculitis in IBD that leads to intestinal ischaemia through vasoconstriction.

Alterations in gastrointestinal motility of diabetic patients have been linked to degenerative changes induced by glucose abnormalities in the peripheral nervous system. The heme oxygenase/carbon monoxide (HO/CO) signalling represents one of the non-adrenergic/non-cholinergic (NANC) neurotransmission pathways involved in regulation of physiological peristalsis. To investigate the role of HO/CO system in intestinal motility under diabetic conditions, the response to electrical field stimulation (EFS) and western blot analysis of HO/CO pathway components were studied on duodenum longitudinal smooth muscle strips isolated from streptozotocin (STZ)-treated diabetic rats (65 mg kg(-1), i.p.) and respective controls (CTRL), 6 weeks after the onset of diabetes. When compared to CTRL, the ability of CO releasing molecule (CORM-3) (100-400 micromol L(-1)) to enhance NANC relaxation was significantly impaired in STZ-treated rats (P < 0.05). Conversely, in vitro incubation with the HO inhibitor ZnPPIX (10 micromol L(-1), 60 min) significantly reduced EFS-induced relaxation in CTRL (P < 0.05), but not in STZ-treated rats. Interestingly, the ability of ZnPPIX to inhibit EFS-induced relaxation was partially restored in STZ-treated rats co-administered in vivo with the HO-1 inducer cobalt protoporphyrin IX (CoPPIX) (0.5 mg per 100 g body weight weekly). Expression of inducible HO-1 protein was increased in homogenates from STZ-treated rats (vs CTRL, P < 0.01), and further increased in STZ-treated rats receiving CoPPIX (P < 0.05). Taken together, our data underline the essential role of HO/CO system in regulation of inhibitory NANC neurotransmission in the duodenum and suggest that dysregulation of HO/CO activity may represent one mechanism by which gastrointestinal motility is altered in diabetes.

In conclusion, our study contributes to further characterize the rat model of indomethacin-induced enteritis and suggests that it is suitable for drug screening in rats, as this model can be obtained in a very short period and is simple and reproducible.