Spontaneous mechanical activity and evoked responses in isolated gastric preparations from normal and dystrophic (mdx) mice

Abstract

This study examined whether alterations of the spontaneous and evoked mechanical activity are present in the stomach of the mdx mouse, the animal model for Duchenne muscular dystrophy. The gastric mechanical activity from whole-organ of normal and mdx mice was recorded in vitro as changes of intraluminal pressure. All gastric preparations developed spontaneous tone and phasic contractions, although the tone of the mdx preparations was significantly greater. Atropine reduced the tone of the two preparations by the same degree. Nomega-nitro-l-arginine methyl ester (l-NAME) significantly increased the tone and spontaneous contractions only in the stomach from normal animals, but did not affect on the mdx preparations. Effects ofl-NAME on tone and contractility were preserved in the presence of tetrodotoxin. In both types of tissues electrical field stimulation (EFS) induced a biphasic response: cholinergic contraction followed by slow relaxation. In nonadrenergic noncholinergic conditions, EFS induced a rapid relaxation followed by a slow component in both types of tissues. l-NAME abolished the rapid component, reduced the slow component and unmasked tachychinergic contractions. No significant difference was found in evoked responses. The enteric neurotransmission is preserved in mdx gastric preparations, although alterations in the ongoing production of nitric oxide are present.

Depression by Relaxin of Neurally Induced Contractile Responses in the Mouse Gastric Fundus1

“…At basal tension, longitudinal strips of gastric fundus appeared mechanically quiescent and did not show spontaneous contractions, as reported in gastric whole-organ in vitro preparations in mice [38]. The lack of spontaneous motor activity in the fundal strips reflects the functional role of this gastric region and implies that activation of muscle contractions in the fundus is dependent on external control, neural, and/or hormonal [39,40].…”

Gastric emptying, small intestinal transit and fecal output in dystrophic (mdx) mice

“…This could be explained assuming that reduced antropyloroduodenal contractility due to the decrease of NO is countered by increased proximal gastric tone, which tends to accelerate gastric emptying of liquids. Indeed, an increase in the gastric tone has been reported previously in mdx mice [21]. Moreover, it has been reported that inhibition of NO synthesis by L-NNA did not slow gastric emptying [31].…”

“…Because changes in gastrointestinal contractility in vitro have been attributed to an impairment of NO [19,[21][22][23][24][25][26], it seems plausible to associate the reduction in the motor small and large intestinal activity to the defective production/release of NO, which increases resistance to flow and decrease transit. In fact, reduced nitrergic relaxation at the level of the small intestine leads to delayed intestinal transit as manifested from studies with NOS-inhibitors in different species illustrating the essential role of NO in intestinal peristalsis [28][29][30].…”

“…Therefore, smooth muscle involvement of the colon, besides immobility and weakness of abdominal wall muscles, might explain the high frequency of constipation that has been reported in DMD patients [16,31]. However, the gastric emptying rate was not delayed in mdx mice, although also in the stomach an impairment of nitric oxide has been reported [21]. This could be explained assuming that reduced antropyloroduodenal contractility due to the decrease of NO is countered by increased proximal gastric tone, which tends to accelerate gastric emptying of liquids.…”

“…Although numerous in vitro studies have indicated that mdx mice experience gastric and intestinal contractility disturbances [18][19][20][21][22], mainly attributed to an impairment of NO [19,[21][22][23][24][25][26], so far investigations on the motor activity of the gut in mdx mouse in vivo conditions have not been performed yet. Therefore, the aim of the present study was to evaluate the possible impact of the dystrophin loss on the gastrointestinal propulsion in mdx mice to assess the presence of motor disturbances.…”