Doga Capanoglu1, Deniz Coskunsever2, Murat Olukman2, Sibel Ülker2, Serhat Bor3. 1. Ege Reflux Group, Section of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Ege University, Bornova, 35100, Izmir, Turkey. 2. Department of Medical Pharmacology, Faculty of Medicine, Ege University, Izmir, Turkey. 3. Ege Reflux Group, Section of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Ege University, Bornova, 35100, Izmir, Turkey. serhatbor@yahoo.com.
Abstract
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.
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 diabeticrabbit 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.
Authors: Brian C Jacobson; Samuel C Somers; Charles S Fuchs; Ciarán P Kelly; Carlos A Camargo Journal: N Engl J Med Date: 2006-06-01 Impact factor: 91.245
Authors: Hashem B El-Serag; Gulchin A Ergun; John Pandolfino; Stephanie Fitzgerald; Thomas Tran; Jennifer R Kramer Journal: Gut Date: 2006-11-24 Impact factor: 23.059
Authors: Leandi Krüger; Tiffany A Pridgen; Ellie R Taylor; Katherine S Garman; Anthony T Blikslager Journal: Am J Physiol Gastrointest Liver Physiol Date: 2020-02-18 Impact factor: 4.052