Role of H2 receptors in the regulation of vascular endothelial growth factor level in experimental peptic ulcer in rats

ABSTRACT

Peptic ulcer is one of the most common clinical diseases. The incidence rate of peptic ulcer has been on the rise over the last two decades. The repair of gastric ulcer requires the reconstitution of epithelial structures and underlying connective tissue, including vessels and muscle layers. This complicated sequence of events requires a high degree of coordination among different cell types, which is regulated by several factors, the most important and best recognized has been vascular endothelial growth factor [VEGF], also some major proinflammatory cytokines namely tumor necrosis factor alpha [TNF-alpha]and interleukin-l0 [lL-10]. This study was carried out to study the role of H2 receptors on the expression of VEGF and proinflammatory cytokines in experimental peptic ulcer using the H2 receptor stimulant [histamine] and H2 receptor blocker [ranitidine]. This study was conducted on 40 adult male albino rats weighing from 200-250 grams each. Animals were divided into 4 groups each of 10 rats namely group 1; normal healthy rats used as control, group 2; rats with experimental peptic ulcer without treatment, group 3; rats with experimental peptic ulcer treated with H2 receptor stimulant histamine, and group 4; rats with experimental peptic ulcer treated with H2 receptor antagonist ranitidine. Rats from all groups were sacrificed on the fourth day after the induction of peptic ulcer. Histamine significantly increased serum VEGF levels in group 3 rats as compared to all other studied groups. Histamine also significantly increased serum IL-10 levels while it decreased serum TNF-alpha in experimental peptic ulcer rats. Ranitidine significantly decreased serum VEGF levels in group 4 rats as compared to histamine treated group 3 rats but showed no significant difference in serum VEGF levels as compared to either to normal control or in untreated peptic ulcer rats. However, ranitidine increased the levels of both serums IL-10 and TNF-alpha as compared to group 2, although it reversed the actions of histamine on both cytokines decreasing IL-10 and increasing TNF-alpha serum levels. It can be concluded that histamine may exhibit protective effect against gastric ulcer through increasing VEGF levels and enhancing angiogenesis. This gastroprotection could be related to stimulation of H2 receptors. Ranitidine could provide gastroprotection through other mechanisms such as the powerful and selective inhibition of gastric acid secretion. However, its effect on VEGF production should be considered.Ranitidine, in combination with histamine, should be extensively studied because it may reduce ulcer. area by reducing inflammatory cytokine levels while increasing gastric mucosal blood flow