Evidences for involvement of nitric oxide in the gastroprotective effect of bromocriptine and cyclosporin A on water immersion stress-induced gastric lesions.

Previous studies have been shown that the adrenergic system involves in gastric secretion and pathogenesis of peptic lesion and activation of alpha(2)-adrenoceptors located on the vagus nerve inhibits gastric acid secretion. Bromocriptine, a dopamine receptor agonist, also has alpha(2) agonistic effect and prevents indomethacin-induced gastric ulcer. alpha(2)-Adrenoceptors involve in the release of nitric oxide which has cytoprotective activity in gastric mucosa. Cyclosporin A (CsA) has also been suppressed stress-induced gastric mucosal lesions, dose dependently. The object of this study was to clarify the interaction between the anti-ulcer effect of bromocriptine (2, 4, 8 mg kg(-1)) or cyclosporin A (5, 10, 20 mg kg(-1)) and nitric oxide. Intraperitoneal injections of bromocriptine and cyclosporin A prevented water immersion stress-induced gastric ulcer in rats. L-Nitro-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, increased stress-induced lesions while L-arginine, a precursor of nitric oxide, decreased these lesions. In conclusion, increasing level of nitric oxide by bromocriptine and cyclosporin A may be one of the contributory factors in their protective effects on gastric mucosa.