title: Esophageal Epithelial Resistance and Lower Esophageal Sphincter Muscle Contraction Increase in a Chronic Diabetic Rabbit Model.
abstract: Esophageal motility disorders and possibly gastroesophageal reflux disease are common in patients with diabetes mellitus.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Ege Reflux Group, Section of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Ege University, Bornova, 35100, Izmir, Turkey.
authors.forename: Doga
authors.initials: D
authors.lastname: Capanoglu
authors.affiliation: Department of Medical Pharmacology, Faculty of Medicine, Ege University, Izmir, Turkey.
authors.forename: Deniz
authors.initials: D
authors.lastname: Coskunsever
authors.affiliation: Department of Medical Pharmacology, Faculty of Medicine, Ege University, Izmir, Turkey.
authors.forename: Murat
authors.initials: M
authors.lastname: Olukman
authors.affiliation: Department of Medical Pharmacology, Faculty of Medicine, Ege University, Izmir, Turkey.
authors.forename: Sibel
authors.initials: S
authors.lastname: Ülker
authors.affiliation: Ege Reflux Group, Section of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Ege University, Bornova, 35100, Izmir, Turkey. serhatbor@yahoo.com.
authors.forename: Serhat
authors.identifier: 0000-0001-5766-9598
authors.initials: S
authors.lastname: Bor
mesh_terms: D000818:Animals; D001786:Blood Glucose; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004848:Epithelium / Q000473:pathology*; D049630:Esophageal Sphincter, Lower / Q000187:drug effects / Q000503:physiopathology*; D004947:Esophagus / Q000473:pathology*; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000503:physiopathology*; D011817:Rabbits
chemical_list: D001786:Blood Glucose; D005947:Glucose
keywords: Diabetes mellitus; Electrical field stimulation; Electrical potential difference; Esophageal muscle contraction; Esophagus; Ussing chambers