Wistar Kyoto rats have impaired gastric accommodation compared to Sprague Dawley rats due to increased gastric vagal cholinergic tone.
OBJECTIVE
Gastric balloon distension shows that, in comparison with Sprague Dawley (SD) rats, Wistar Kyoto (WKY) rats have a decreased volume response owing to a lower accommodation rate. The aim of this study was to compare the role of the vagal cholinergic and nitrergic pathways in the accommodation reflex in these rat strains.


METHODS
The volume response to ramp-tonic gastric balloon distension was pharmacologically manipulated by using L-NAME 25 mg/kg i.v., molsidomine 20 mg/kg i.p., atropine 1 mg/kg i.v. and clonidine 0.7 mg/kg s.c.


RESULTS
Following L-NAME, the maximal volume response to distension was significantly decreased in WKY rats (0.74+/-0.11 ml versus 1.18+/-0.13 ml) whereas only a tendency to such a decrease was seen in SD rats. The NO donor molsidomine significantly increased the volume in SD rats (4.91+/-0.46 ml versus 1.81+/-0.50 ml) but only weakly in WKY rats. Atropine significantly increased the gastric volume in WKY rats (2.78+/-0.29 ml versus 1.00+/-0.17 ml) but not in SD rats. Clonidine increased the accommodation rate in the WKY rat, resulting in increased maximal volume (1.69+/-0.26 ml versus 0.65+/-0.11 ml) indicating a reduction in acetylcholine release as a consequence of stimulated presynaptic adrenergic receptors on cholinergic neurons.


CONCLUSIONS
The results indicate that WKY rats may have an increased gastric vagal cholinergic drive, which, during distension, masks the relaxing effect of NO-releasing neurons. The findings in WKY rats could be of relevance for functional dyspeptic patients with impaired gastric accommodation to meals.
Nielsen
Maria Astin
MA
Department of Integrative Pharmacology, AstraZeneca R&D Mölndal, SE-431 83 Mölndal, Sweden. Maria.Astin@astrazeneca.com
Bayati
Alfred
A
Mattsson
Hillevi
H
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D008981:Molsidomine / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY / Q000502:physiology*; D017207:Rats, Sprague-Dawley / Q000502:physiology*; D017208:Rats, Wistar; D013270:Stomach / Q000187:drug effects / Q000294:innervation* / Q000502:physiology*; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D001285:Atropine; D008981:Molsidomine; D003000:Clonidine; D019331:NG-Nitroarginine Methyl Ester