1Ahmed M El Gohary, 1Hoda A El-Aggan, 2Nahed M Baddour, 3Amal F Ketat and 1Reem M Farouk.
Departments of 1Medicine (Hepatobiliary Unit), 2Pathology and 3Medical Biochemistry, Faculty of Medicine, University of Alexandria, Egypt.
Portal hypertensive gastropathy (PHG) has distinct morphological and functional abnormalities, which may be related to the hemodynamic changes in cirrhosis. The aim of the present study was to assess the gastric microvascular changes and epithelial proliferation in cirrhotic patients with and without PHG in relation to two vasoactive molecules; nitric oxide (NO) and endothelin-1 (ET-1). To achieve this goal, 42 patients with cirrhosis (16 with severe PHG, 14 with mild PHG and 12 without PHG) and 13 healthy subjects (control group) were included in the study. Endoscopic gastric mucosal biopsies (fundic and/or corporeal and antral) were assessed for microvascular changes by morphometric analysis of sections stained with monoclonal antibodies to vascular endothelial cell adhesion molecule-1 (VCAM-1) and gastric epithelial proliferation using immunostaining for proliferating cell nuclear antigen (PCNA). Also, serum levels of nitrite and nitrate, an index of NO production, and plasma endothelin-1 (ET-1) concentration were measured in all cirrhotic patients and controls. Examination of the fundic and corporeal gastric biopsies showed a significant increase in the total vascular area, number of vessels and vessel wall thickness and a significant decrease in the PCNA-labelling index in cirrhotic patients with severe and mild PHG compared with those without PHG and control subjects (P < 0.05). In antral mucosa, these changes were only evident in patients with severe PHG (P < 0.05). Serum nitrite and nitrate levels showed a significant stepwise increase in cirrhotic patients without PHG, through patients with mild PHG, to patients with severe PHG as compared with control subjects (P < 0.05). Plasma ET-1 concentration was significantly higher in patients with cirrhosis regardless of the presence of PHG than in control subjects (P < 0.05), without statistically significant differences between cirrhotic patients with and without PHG (P > 0.05). The levels of serum nitrite and nitrate but not of plasma ET-1 showed a direct correlation with the gastric morphometric microvascular changes and an inverse correlation with the PCNA-labelling index of the fundic and corporeal mucosa in cirrhotic patients (P < 0.01). In conclusion, the results of the present study suggest that excessive production of NO (but not of ET-1) in patients with cirrhosis is likely to be involved in the vasodilation of gastric vessels and the inhibition of gastric epithelial proliferation in PHG. Therefore, treatment with NO inhibitors may ameliorate the pathophysiological abnormalities of the portal hypertensive gastric mucosa.