Cigarette smoking delays ulcer healing: role of constitutive nitric oxide synthase in rat stomach

Epidemiological studies have shown that cigarette smoking is associated with peptic ulceration. This study aims to investigate the mechanisms by which cigarette smoking delays ulcer healing in rats. Gastric ulcers were induced by applying acetic acid to the luminal surfaces in rats. Twenty-four hours later, rats were exposed to different concentrations of cigarette smoke (0, 2, or 4%) for a 1-h period once daily for 3 or 6 days. Cigarette smoke exposure delayed ulcer healing and decreased gastric blood flow and angiogenesis at the ulcer margin. These changes were accompanied by a significant reduction of constitutive nitric oxide synthase (cNOS) activity but not PGE2 production and vascular endothelial growth factor levels. Administration of L-arginine (10 mg/kg iv) completely reversed the adverse actions on ulcer healing, gastric blood flow, and angiogenesis in the mucosa at the ulcer margin but partially restored angiogenesis in granulation tissues. In conclusion, cigarette smoke exposure delays ulcer healing through depression of gastric blood flow and angiogenesis at the ulcer margin. Reduction of cNOS expression and activity is suggested to be involved in these ulcerogenic processes.published_or_final_versio

Mechanistic study of adverse actions of cigarette smoke exposure on acetic acid-induced gastric ulceration in rats

Cigarette smoking is associated with peptic ulceration in humans. A mechanistic study of the potentiating effects of cigarette smoking on acetic acid-induced gastric ulceration in rats was hence performed. Rats were exposed to 0, 2 or 4% of cigarette smoke for three 1-hr periods during the 24 hr starvation before ulcer induction. Cigarette smoke exposure potentiated ulcer formation which was accompanied by a reduction of gastric blood flow at the ulcer base and ulcer margin. Further studies showed that cigarette smoke exposure alone did not cause any macroscopic injury in the stomach but significantly decreased the basal gastric blood flow in a concentration-dependent manner, which was coupled with an increase in mucosal xanthine oxidase (XO) activity. Pretreatment with allopurinol (Allo, 5 mg/kg, iv), a XO inhibitor, partially prevented the potentiating effect of cigarette smoke exposure on ulcer formation and also significantly improved the gastric blood flow. Ulcer induction itself dramatically increased constitutive nitric oxide synthase (cNOS) activity and prostaglandin E2 (PGE2) level in the gastric mucosa. However, the increment of cNOS activity but not PGE2 level was markedly attenuated by cigarette smoke exposure. Sodium nitroprusside (SNP, 25 or 50 μg/kg, iv), a nitric oxide (NO) donor, completely abolished the potentiating effect of cigarette smoke exposure on ulcer formation and also reversed the adverse effect on gastric blood flow. Thus, XO activation and cNOS reduction in the gastric mucosa are closely associated with the potentiating action of cigarette smoke exposure on ulcer formation in rats

An experimental model for studying passive cigarette smoking effects on gastric ulceration

Cigarette smoking is associated with gastric mucosal damage in humans. For this study, a smoke chamber was designed to investigate the effects of passive smoking on gastric ulceration. Different concentrations of cigarette smoke (0%, 1%, 2%, and 4%) were perfused into a chamber for one hr in which conscious rats were placed. This one-hr smoke exposure potentiated ethanol (70%, v/v, p.o.)-induced gastric mucosal damage and increased serum nicotine levels; however, it did not affect the blood pH, pCO2, pO2, and HCO3 concentrations, or the systemic blood pressure and heart rate. Under these experimental conditions, exposure to cigarette smoke produced no significant changes in the blood acid/base balance and stress in the animals but significantly potentiated ethanol-induced gastric mucosal damage. The present experimental model is suitable for studying the adverse interactions between passive smoking and alcohol drinking in gastric ulcer formation in rats

Role of capsaicin sensory nerves and EGF in the healing of gastric ulcer in rats

Accumulating evidence indicates that capsaicin sensitive afferent fibers play a pivotal role not only in gastroprotection but also in ulcer healing. Denervation of capsaicin sensitive afferent fibers exerts an adverse action on these effects. However, whether such an action is mediated through a depression on epidermal growth factor (EGF) is underfined. In this study, the effects of denervation of sensory neurons with capsaicin (100 mg/kg, s.c.) on acetic acid-induced chronic gastric ulcers and their relationship with the EGF expression in salivary glands, serum and gastric mucosa were investigated. Capsaicin significantly increased ulcer size, decreased gastric mucosal cell proliferation at the ulcer margin, angiogenesis in the granulation tissue and also gastric mucus content. Ulcer induction by itself dramatically elevated EGF levels in salivary glands and serum on day 1 and 4, and also in the gastric mucosa on day 4. However, capsaicin completely abolished these effects. It is concluded that stimulation of EGF expression in salivary glands and serum may be one of the mechanisms by which capsaicin sensitive nerves contribute to the gastroprotective and ulcer healing actions in the stomach. (C) 2000 Elsevier Science Inc.link_to_subscribed_fulltex