Nerve‐induced release of nitric oxide in the rabbit gastrointestinal tract as measured by in vivo microdialysis

Abstract

Nitric oxide (NO) has been suggested as a gastrointestinal neurotransmitter, mediating the gastric receptive relaxation and the relaxation in the peristaltic reflex. The aim of the present study was to measure nerve‐induced NO formation in vivo in the gastrointestinal tract. Formation of the nitric oxide oxidation products nitrite and nitrate during vagal nerve stimulation were measured in the anaesthetized rabbit. Microdialysis probes were inserted into the wall of the stomach and proximal colon, and nitrite and nitrate in dialysate measured by capillary electrophoresis. During bilateral vagal nerve stimulation there was an increase in nitrite and nitrate formation at the level of the stomach and in nitrite formation at the level of the colon. This increase was inhibited by intravenous administration of the NO synthase inhibitor N^ω‐nitro‐L‐arginine methyl ester (l‐NAME 30 mg kg⁻¹). Furthermore, L‐NAME significantly increased nerve‐induced gastric and colonic contractions, as well as spontaneous colonic contractions. In summary, we present a new methodological procedure for quantification of small changes in nitric oxide formation in vivo. This study provides evidence that nitric oxide is released in the stomach and colonic wall during vagal nerve activity, at concentrations able to cause inhibition of smooth muscle contractions in vivo.