Published in:
01-07-2016 | Original Article
Esophageal Epithelial Resistance and Lower Esophageal Sphincter Muscle Contraction Increase in a Chronic Diabetic Rabbit Model
Published in: Digestive Diseases and Sciences | Issue 7/2016
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Background
Esophageal motility disorders and possibly gastroesophageal reflux disease are common in patients with diabetes mellitus.
Aims
We aimed to investigate both the electrophysiological characteristics of the esophageal epithelium and the contractility of the lower esophageal sphincter (LES) muscle in alloxane-induced diabetic rabbits.
Methods
Electrophysiological properties were measured using an Ussing chamber method. An acid-pepsin model was employed with pH 1.7 or weakly acidic (pH 4) Ringer and/or pepsin. Smooth muscle strips of the LES were mounted in an isolated organ bath. Contractile responses to an electrical field stimulation and cumulative concentrations of acetylcholine were recorded. Contractility of the muscle strips were tested in the presence of Rho-kinase inhibitor (Y-27632) and nonspecific nitric oxide inhibitor (L-NAME).
Results
The resistance of diabetic tissue perfused in the pH 1.7 Ringer decreased 17 %; pepsin addition decreased it by 49 %. The same concentrations caused a more distinct loss of resistance in the control tissues (22 and 76 %, p < 0.05). The perfusion of tissues in increased concentrations of luminal and serosal glucose did not change the tissue resistance and voltage. Diabetes significantly increased both the electrical field stimulation and acetylcholine-induced contractions in the LES muscle strips (p < 0.01). Incubation with Y-27632 significantly decreased the acetylcholine-induced contractions in a concentration-dependent manner (p < 0.01).
Conclusions
The acid-pepsin model in the diabetic rabbit esophageal tissue had less injury compared with the control. The diabetic rabbit LES muscle had higher contractility, possibly because of the activation of the Rho-Rhokinase pathway. Our results show that in a chronic diabetic rabbit model the esophagus resists reflux by activating mechanisms of mucosal defense and increasing the contractility of the LES.