Nitric oxide regenerates the normal colonic peristaltic activity in mdx dystrophic mouse

• Published in: Neuroscience letters 1999-02, Vol.261 (1), p.9-12
• Main Authors: Azzena, Gian Battista, Mancinelli, Rino
• Format: Article
• Language: English
• Subjects: Animals; Arginine - pharmacology; Biological and medical sciences; Colon - innervation; Colon - physiology; Diseases of striated muscles. Neuromuscular diseases; Enteric nervous system; Enteric Nervous System - physiology; Enzyme Inhibitors - pharmacology; In Vitro Techniques; mdx mouse; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Inbred mdx; Motor Neurons - physiology; Muscle, Smooth - drug effects; Muscle, Smooth - innervation; Muscle, Smooth - physiology; Muscular dystrophy; Muscular Dystrophy, Animal - metabolism; Neurology; NG-Nitroarginine Methyl Ester - pharmacology; Nitric oxide; Nitric Oxide - metabolism; Peristalsis - drug effects; Peristalsis - physiology; Peristaltic activity; Smooth muscle
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/S0304-3940(98)00993-8

We demonstrated in vitro that the colonic peristaltic activity is modified in dystrophin-deficient mdx mouse indicating a defect in the enteric nervous system (ENS). Since nitric oxide (NO) has been proposed as a putative inhibitory mediator of ENS, here we have examined the effects of both l-Arginine ( l-Arg) and N ω -nitro- l-arginine methyl ester ( l-NAME) on the peristaltic activity of mdx mouse distal colon. The motor pattern of colonic segment showed irregular peristaltic waves. l-Arg (10 −7–10 −5 M) induced the peristaltic activity to slow down. At a concentration of 10 −5 M, l-Arg produced hypomotility, characterised by a decrease in amplitude, frequency and ejected fluid volume. Conversely, l-NAME elicited hypermotility, this effect being reversed once again by the subsequent addition of l-Arg. Interestingly the addition of 10 −5 M l-Arg to the organ bath led to the normal progression, in an oral to aboral direction, of 90% of the peristaltic waves. This last result strongly suggests that exogenous application of l-Arg restores the integrative circuits of the ENS responsible for programming and co-ordinating peristaltic activity in the distal colon of mdx mouse.