Pyloric motor responses to central and peripheral nitric oxide in the ferret

Abstract

This study has investigated the relative importance of central nervous and peripheral nitroxidergic mechanisms in the control of pyloric motility. In 10 urethane-anaesthetized ferrets, drugs were administered directly to the CNS via a 0.5-mm-diameter cannula inserted into the 4th ventricle, approximately at the obex. Drugs were also given directly to the upper GI tract by close intra-arterial (i.a.) injection at the coeliac axis. Antropyloroduodenal pressures were recorded with a five-channel sleeve/sidehole micromanometric assembly (1.35 × 1.75 mm o.d.), which was introduced via the duodenum. Pyloric motility was stimulated throughout the main part of each study with a continuous i.v. infusion of CCK-8 (30 pmol min−1). This infusion produced an immediate and sustained increase in tonic and phasic pyloric activity, and sustained abolition of antral pressure waves. CCK-8 also induced a duodenal motor response, but this was short-lived (11.4 ± 7.9 min). Coeliac axis injection of the NO donor S-nitroso-N-acetyl-penicillamine (SNAP) decreased phasic pyloric activity (from 330 ± 35 to 148 ± 21 mmHg min−1 after SNAP 5 μg, P < 0.01). By comparison, central SNAP administration over the same dose range had no effect on CCK-stimulated pyloric motility. Inhibition of endogenous NO synthase with L-Nitro Arginine Methyl Ester (L-NAME, 100 mg kg−1 close i.a.) caused a marked increase of phasic pyloric motor activity from 349 ± 59 to 1044 ± 140 mmHg min−1 (P < 0.01). In addition, SNAP caused marked stimulation of pyloric tone from 2.6 ± 0.5 to 13.1 ± 2.8 mmHg (P < 0.01). Central nervous administration of L-NAME caused modest enhancement of phasic pyloric activity (248 ± 31 to 283 ± 32 mmHg min−1 P < 0.05) and pyloric tone (2.6 ± 0.5 to 3.7 ± 0.7 mmHg, P < 0.05). Our data indicate that motor activity of the ferret pylorus is potently modulated by NO released within the upper gut. Additionally, there is potential for modulation of pyloric motility by central nervous system production of NO.