Gastric distension-induced pyloric relaxation: central nervous system regulation and effects of acute hyperglycaemia in the rat

1. The pylorus plays an important role in the regulation of gastric emptyin g. In addition to the autonomic neuropathy associated with long-standing di abetes, acute hyperglycaemia per se has effects on gastric emptying. In thi s study, the role of the central nervous system in modulating the effects o f hyperglycaemia on gastric distension-induced pyloric relaxation was inves tigated. 2. Gastric distension-induced pyloric relaxation was significantly reduced by subdiaphragmatic vagotomy, hexamethonium (20 mg kg(-1)) and N-G-nitro-L- arginine methyl ester (L-NAME; 10 mg kg(-1)), a nitric oxide synthase (NOX) biosynthesis inhibitor, in anaesthetized rats. In contrast, neither splanc hnectomy nor guanethidine (5 mg kg(-1)) had an effect. 3. An intravenous (I.V.) infusion of D-glucose (20 %) for 30 min, which inc reased blood glucose concentrations from 5.4 to 12.8 mM, significantly inhi bited gastric distension-induced pyloric relaxation. 4. An intracerebroventricular (I.C.V.) injection of D-glucose (3 mu mol) al so significantly inhibited gastric distension-induced pyloric relaxation wi thout affecting peripheral blood glucose concentrations. 5. I.V. infusion of D-glucose significantly elevated hypothalamic neuropept ide Y (NPY) concentrations. 6. Intracerebroventricular (I.C.V.) administration of NPY (0.03-3 nmol) and a Y1 receptor agonist, [leu(31), pro(34)] Npy (0.03-3 nmol), significantly inhibited gastric distension-induced pyloric relaxation in a dose-dependen t manner. 7. I.C.V. administration of a Y1 receptor antagonist, BIBP 3226 (30 nmol), and of a NPY antibody (titre 1:24 000, 3 mul) abolished the inhibitory effe cts of hyperglycaemia on gastric distension-induced pyloric relaxation. 8. Taken together, these findings suggest that gastric distension-induced p yloric relaxation is mediated via a vago-vagal reflex and NO release. Acute hyperglycaemia stimulates hypothalamic NPY release, which, acting through the Y1 receptor, inhibits gastric distension-induced pyloric relaxation in rats exposed to acute elevations in blood glucose concentrations.