Are humoral factors involved in the colonic mucosal lesion in portal hypertensive rats ?

Aims : With a prehepatic portal hypertensive rat model, we explored the involvement of humoral factors to the occurrence of portal hypertensive colopathy (PHC), another clinical entity besides portal hypertensive gastropathy (PHG) in portal hyper- tension, by investigating the expression of inducible nitric oxide synthase (iNOS), endothelial constitutive NOS (ecNOS), endothe- lin-1 (ET-1), tumour necrosis factor alpha (TNF-a) and vascular endothelial growth factor (VEGF) in the colonic and gastric mucosa. Methods : Portal hypertension was produced by a two-stage lig- ation of portal vein plus ligation of the left adrenal vein in male Sprague-Dawley rats. Two weeks after complete obstruction of the portal vein, the portal pressure was measured and the expression of iNOS, ecNOS, ET-1, TNF-a and VEGF in the colonic and gas- tric mucosa were detected by RT-PCR and immunohistochemistry methods. Results : A 1.8fold (P < 0.01) elevation of the portal pressure was detected in the portal hypertensive rats as compared to control. Significantly up-regulation of the mRNA levels of iNOS (P < 0.01), ET-1 (P < 0.05) and TNF-a (P < 0.01), but not ecNOS and VEGF, were detected in the colonic mucosa of portal hypertensive rats compared with control. The mRNA of iNOS, ecNOS, ET-1, TNF-a and VEGF were all significantly increased at varied levels in the gastric mucosa as compared to control (P all < 0.05). No difference of the appearance and localization of immunostaining of iNOS, ecNOS, ET-1, TNF-a and VEGF in the colonic and gastric mucosa were seen between two groups. Conclusions : These data suggest the involvement of the up- regulation of iNOS, ET-1 and TNF-a in the colonic mucosal lesion of portal hypertensive rats. (Acta gastroenterol. belg., 2007, 70, 271- 276).