Gastric distension-induced pyloric relaxation: central nervous system regulation and effects of acute hyperglycaemia in the rat
Corresponding author T. Takahashi: Surgical Service 112, Durham VA Medical Center, Durham, NC 27705, USA. Email: firstname.lastname@example.org
- 1The pylorus plays an important role in the regulation of gastric emptying. In addition to the autonomic neuropathy associated with long-standing diabetes, acute hyperglycaemia per se has effects on gastric emptying. In this study, the role of the central nervous system in modulating the effects of hyperglycaemia on gastric distension-induced pyloric relaxation was investigated.
- 2Gastric distension-induced pyloric relaxation was significantly reduced by subdiaphragmatic vagotomy, hexamethonium (20 mg kg−1) and NG-nitro-L-arginine methyl ester (L-NAME; 10 mg kg−1), a nitric oxide synthase (NOS) biosynthesis inhibitor, in anaesthetized rats. In contrast, neither splanchnectomy nor guanethidine (5 mg kg−1) had an effect.
- 3An intravenous (I.V.) infusion of D-glucose (20 %) for 30 min, which increased blood glucose concentrations from 5.4 to 12.8 mM, significantly inhibited gastric distension-induced pyloric relaxation.
- 4An intracerebroventricular (I.C.V.) injection of D-glucose (3 μmol) also significantly inhibited gastric distension-induced pyloric relaxation without affecting peripheral blood glucose concentrations.
- 5I.V. infusion of D-glucose significantly elevated hypothalamic neuropeptide Y (NPY) concentrations.
- 6Intracerebroventricular (I.C.V.) administration of NPY (0.03-3 nmol) and a Y1 receptor agonist, [leu31, pro34] NPY (0.03-3 nmol), significantly inhibited gastric distension-induced pyloric relaxation in a dose-dependent manner.
- 7I.C.V. administration of a Y1 receptor antagonist, BIBP 3226 (30 nmol), and of a NPY antibody (titre 1:24 000, 3 μl) abolished the inhibitory effects of hyperglycaemia on gastric distension-induced pyloric relaxation.
- 8Taken together, these findings suggest that gastric distension-induced pyloric 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.