ROLE OF NITRIC-OXIDE IN REGULATION OF GASTRIC-ACID SECRETION IN RATS - EFFECTS OF NO DONORS AND NO SYNTHASE INHIBITOR

1. The role of nitric oxide (NO) in the regulation of acid secretion w as examined in the anaesthetized rat. 2. A rat stomach was mounted in an ex vivo chamber, instilled with 2 ml of saline every 15 min, and th e recovered sample was titrated at pH 7.0 against 0.1 N NaOH by use of an automatic titrator for acid secretion. Gastric mucosal blood flow (GMBF) was measured simultaneously by laser Doppler flowmeter. 3. Intr agastric application of NO donors such as FK409 (3 and 6 mg ml(-1)) an d sodium nitroprusside (SNP; 6 and 12 mg ml(-1)) as well as i.p. admin istration of cimetidine (60 mg kg(-1)), a histamine H-2-receptor antag onist, significantly inhibited the increase in acid secretion in respo nse to pentagastrin (60 mu g kg(-1) h(-1), i.v.), in doses that increa sed gastric mucosal blood flow (GMBF). 4. Intragastric application of FK409 (6 mg ml(-1)) increased both basal and stimulated acid secretion induced by YM-14673 (0.3 mg kg(-1), i.v.), an analogue of thyrotropin -releasing hormone (TRH), but had no effect on the acid secretory resp onse induced by histamine (4 mg kg(-1) h(-1), i.v.). 5. Pretreatment w ith N-G-nitro-L-arginine methyl ester (L-NAME, 10 mg kg(-1), i.v.) did not affect basal acid secretion, but significantly potentiated the in crease in acid secretion induced by YM-14673 and slightly augmented th e acid secretory response to pentagastrin. 6. Both pentagastrin and YM -14673 increased the release of nitrite plus nitrate (NOx), stable NO metabolites, into the gastric lumen, and these changes were completely inhibited by prior administration of L-NAME (10 mg kg(-1), i.v.). 7. Pentagastrin caused an increase in luminal release of histamine and th is response was significantly suppressed by intragastric application o f FK409 (6 mg ml(-1)). 8. These results suggest that either exogenous or endogenous NO has an inhibitory action on gastric acid secretion th rough suppression of histamine release from enterochromaffin-like (ECL ) cells.