EFFECTS OF THE SELECTIVE I-1 IMIDAZOLINE RECEPTOR AGONIST, MOXONIDINE, ON GASTRIC-SECRETION AND GASTRIC-MUCOSAL INJURY IN RATS

1 Previous reports of the effects of alpha(2)-adrenoceptor stimulation on gastric secretion are inconsistent because it was not clear whethe r the compounds were activating alpha(2)-adrenoceptors and/or newly de scribed imidazoline receptors. In the present experiments, the effects of moxonidine, an I-1-imidazoline receptor agonist and antihypertensi ve agent, on gastric secretion and on experimental gastric mucosal inj ury were examined. 2 Moxonidine (0.01, 0.1 and 1.0 mg kg(-1), i.p.) po tently inhibited basal (non-stimulated) gastric acid secretion in cons cious rats with an ED(50) of 0.04 mg kg(-1). Two hours following admin istration of the highest dose of moxonidine (1.0 mg kg(-1)), gastric a cid output was completely suppressed. Moxonidine also significantly in creased intragastric pH, at the two highest doses. 3 The alpha(2)-adre noceptor agonist, clonidine (0.01, 0.1 and 1.0 mg kg(-1), i.p.) decrea sed basal acid secretion at the lowest dose (37%) and at the highest d ose (46%), while the intermediate dose did not affect gastric acid out put. 4 In an ethanol-induced model of gastric mucosal injury, moxonidi ne decreased the length of lesions at the lowest and highest doses (0. 01 and 1.0 mg kg(-1)) as well as the number of the lesions, at the hig hest dose (1.0 mg kg(-1)). 5 In pylorus-ligated rats, moxonidine signi ficantly decreased acid secretion (all doses), total secretory volume (1.0 mg kg(-1)) as well as pepsin output (1.0 mg kg(-1)). 6 In compari son to clonidine, moxonidine appears to be a more potent anti-secretor y and gastric-protective compound. These data indicate a potential rol e for imidazoline receptor agonists in the management of gastroduodena l diseases associated with hypertension. The relative contribution of the central and peripheral effects of moxonidine to these gastrointest inal actions remains to be determined.