title: Characterisation of colonic accommodation in Wistar Kyoto rats with impaired gastric accommodation.
abstract: Defective colonic and gastric accommodations have been related to altered viscerosensitivity in irritable bowel syndrome and to functional dyspepsia, respectively. We assessed colonic accommodation in rats with impaired gastric accommodation to determine if altered accommodation can be regarded as a widespread pathophysiological alteration within the gastrointestinal (GI) tract. Colonic accommodation during colorectal distension (CRD) was assessed in Wistar Kyoto rats (WKY), an animal model of impaired gastric accommodation, and in Sprague-Dawley (SD) and Wistar rats, considered normal. CRD (10-80 mmHg)-induced visceral pain responses were also evaluated in the same strains of rats. During gastric distension, WKY rats had lower intra-gastric volume (0.96 +/- 0.22 ml) than SD (1.85 +/- 0.19 ml, P < 0.05) or Wistar rats (2.80 +/- 0.26 ml, P < 0.05), indicating impaired gastric accommodation. In the same animals, pressure-volume curves were constructed during CRD as a measure of colonic accommodation. During short-lasting (1 min) phasic CRD (2-20 mmHg), the pressure-volume curve in WKY rats was displaced to the right compared with SD or Wistar rats, indicative of reduced colonic accommodation (maximal volume: SD, 1.22 +/- 0.05 ml; Wistar, 1.07 +/- 0.04 ml; WKY, 0.87 +/- 0.07 ml; P < 0.01). Pre-treatment with atropine normalised the pressure-volume responses in WKY rats. No differences among strains were observed during the 2-min phasic or ramp-tonic CRD. Visceral pain responses during CRD (10-80 mmHg) were, overall, similar in the three strains, although WKY rats showed lower thresholds for pain (28.0 +/- 4.9 mmHg) than SD (42.3 +/- 6.6 mmHg, P = 0.072) or Wistar rats (48.3 +/- 6.0 mmHg, P < 0.05). WKY rats, although having impaired gastric accommodation, have the ability to fully accommodate the colon to increasing pressures. In WKY rats, impaired accommodation of the smooth muscle might not be a widespread phenomenon along the GI tract but rather a local disturbance.
authors.affiliation: Department of Integrative Pharmacology-Gastrointestinal Biology, AstraZeneca R&D, Mölndal SE-431 83, Sweden. vicente.martinez@astrazeneca.com
authors.forename: Vicente
authors.initials: V
authors.lastname: Martínez
authors.forename: Mikael
authors.initials: M
authors.lastname: Ryttinger
authors.forename: Marita
authors.initials: M
authors.lastname: Kjerling
authors.forename: Maria
authors.initials: M
authors.lastname: Astin-Nielsen
mesh_terms: D015746:Abdominal Pain; D000818:Animals; D003106:Colon / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D041981:Gastrointestinal Tract / Q000503:physiopathology; D043183:Irritable Bowel Syndrome / Q000503:physiopathology*; D009929:Organ Size; D011312:Pressure; D051381:Rats; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013270:Stomach / Q000503:physiopathology*