PYLORIC MOTOR RESPONSE TO CENTRAL AND PERIPHERAL NITRIC-OXIDE IN THE FERRET

This study has investigated the relative importance of central nervous and peripheral nitroxidergic mechanisms in the control of pyloric mot ility. In 10 urethane-anaesthetized ferrets, drugs were administered d irectly 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 x 1.75 mm o.d.) , which was introduced via the duodenum. Pyloric motility was stimulat ed throughout the main part of each study with a continuous i.v. infus ion of CCK-8 (30 pmol min(-1)). This infusion produced an immediate an d sustained increase in tonic and phasic pyloric activity, and sustain ed abolition of antral pressure waves. CCK-8 also induced a duodenal m otor response, but this was short-lived (11.4 +/- 7.9 min). Coeliac ax is injection of the NO donor S-nitroso-N-acetyl-penicillamine (SNAP) d ecreased phasic pyloric activity (from 330 +/- 35 to 148 +/- 21 mmHg m in(-1) after SNAP 5 mu g, P < 0.01). By comparison, central SNAP admin istration over the same dose range had no effect on CCK-stimulated pyl oric motility. Inhibition of endogenous NO synthase with L-Nitro Argin ine Methyl Ester (L-NAME, 100 mg kg(-1) close i.a.) caused a marked in crease of phasic pyloric motor activity from 349 +/- 59 to 1044 +/- 14 0 mmHg min(-1) (P < 0.02). In addition, SNAP caused marked stimulation of pyloric tone from 2.6 +/- 0.5 to 13.1 +/- 2.8 mmHg (P < 0.02). Cen tral nervous administration of L-NAME caused modest enhancement of pha sic 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 modula ted by NO released within the upper gut. Additionally, there is potent ial for modulation of pyloric motility by central nervous system produ ction of NO.