Role of nitric oxide and prostaglandins in histamine-induced lesions in devascularized rat stomachs.

We recently established a new method to induce gastric lesions by administering histamine to rats with partially devascularized stomach and ligated-pylorus. This study examined the pathogenic mechanism of gastric lesion formation in this procedure. Methods: Male Wistar rats were used after fasting. Under ether anesthesia, the gastric artery and the accompanying venous were ligated for partial devascularization of the stomach. The pylorus was ligated concurrently. Ten minutes later, histamine 2HCl (40 mg/kg) was administered sc twice (every 2 hours); the animals were killed 4 hours later. Gastric contents were analyzed for acid output, and the damaged area was determined under a dissecting microscope. Results: Histamine significantly increased gastric acid secretion in normal rats with pylorus ligation alone. In contrast, similar treatment with histamine to rats with devascularized stomachs and ligated-pylorus did not stimulate gastric acid secretion compared with the control group. Nonetheless, severe mucosal damages were observed in the oxyntic area in the anterior and posterior walls in ali animals. Histamine H2 receptor antagonists, given po 1h before pylorus ligation, significantly inhibited the lesion formation in a dose-related manner. The lesion formation was inhibited despite the absence of suppression of acid secretion. Histamine H1 receptor antagonists significantly inhibited the development of lesions. Gastric acid secretion was significantly increased in the HI blocker treated-group. Such results suggest that gastric acid is not involved in the mechanism for the development of these lesions. NOS inhibitor significantly inhibited the development of lesions, while iNOS inhibibor (aminoguanidine, sc) had no effect on lesion formation. The development of lesions was also inhibited by pretreatment with indomethacin (sc). Conclusion: The mechanism by which histamine induces gastric lesions in the above model appears to involve the ischemia-reperfusion... [ABSTRACT FROM AUTHOR]