NITRIC-OXIDE MEDIATES THE INHIBITION BY INTERLEUKIN-1-BETA OF PENTAGASTRIN-STIMULATED RAT GASTRIC-ACID SECRETION

Bolus injection of interleukin-1beta (2 mug kg-1, i.v.) inhibited acid secretion induced by intravenous infusion of pentagastrin (8 mug kg-1 h-1) in the continuously perfused stomach of the anaesthetized rat. Administration of interleukin-1beta did not modify mean systemic arterial blood pressure. Pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME, 2-10 mg kg-1, i.v.), but not dexamethasone (5 mg kg-1, s.c. twice over 16 h), restored the acid secretory responses to pentagastrin. The actions of L-NAME were reversed by the prior administration Of L-arginine (100 mg kg-1, i.v.), but not by its enantiomer D-arginine (100 mg kg-1, i.V.). L-NAME (5 mg kg-1, i.v.) increased blood pressure but this was not the mechanism by which interleukin-induced acid inhibition was prevented, since similar systemic pressor responses induced by phenylephrine (10 mug kg-1 min-1, i.v.), had no such effect. These findings suggest that interleukin-induced inhibition of acid responses to pentagastrin involves synthesis of NO from L-arginine.