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

J Physiol. 2001 Jun 15;533(Pt 3):801-13. doi: 10.1111/j.1469-7793.2001.t01-1-00801.x.


1. The 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. 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 (NOS) biosynthesis inhibitor, in anaesthetized rats. In contrast, neither splanchnectomy nor guanethidine (5 mg kg(-1)) had an effect. 3. An 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. 4. An intracerebroventricular (I.C.V.) injection of D-glucose (3 micromol) also significantly inhibited gastric distension-induced pyloric relaxation without affecting peripheral blood glucose concentrations. 5. I.V. infusion of D-glucose significantly elevated hypothalamic neuropeptide 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-dependent 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 microl) abolished the inhibitory effects of hyperglycaemia on gastric distension-induced pyloric relaxation. 8. Taken 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Animals
  • Arginine / analogs & derivatives*
  • Arginine / pharmacology
  • Catheterization
  • Central Nervous System / physiopathology*
  • Electrophysiology
  • Hyperglycemia / physiopathology*
  • Hypothalamus / metabolism
  • Injections, Intraventricular
  • Male
  • Muscle Relaxation / drug effects
  • Muscle Relaxation / physiology
  • Muscle, Smooth / physiology
  • Neuropeptide Y / metabolism
  • Neuropeptide Y / pharmacology
  • Pylorus / physiopathology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Neuropeptide Y / antagonists & inhibitors
  • Reference Values
  • Stomach / physiopathology*


  • BIBP 3226
  • Neuropeptide Y
  • Receptors, Neuropeptide Y
  • Arginine