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

We demonstrated in vitro that the colonic peristaltic activity is modified in dystrophin-deficient mdx mouse indicating a defect in the enteric nervou s system (ENS). Since nitric oxide (NO) has been proposed as a putative inh ibitory mediator of ENS, here we have examined the effects of both L-Argini ne (L-Arg) and N-omega-nitro-L-arginine methyl ester (L-NAME) on the perist altic activity of mdx mouse distal colon. The motor pattern of colonic segm ent 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 p roduced hypomotility, characterised by a decrease in amplitude, frequency a nd ejected fluid volume. Conversely, L-NAME elicited hypermotility, this ef fect being reversed once again by the subsequent addition of L-Arg. Interes tingly the addition of 10(-5) M L-Arg to the organ bath led to the normal p rogression, in an oral to aboral direction, of 90% of the peristaltic waves . This last result strongly suggests that exogenous application of L-Arg re stores the integrative circuits of the ENS responsible for programming and co-ordinating peristaltic activity in the distal colon of mdx mouse. (C) 19 99 Elsevier Science Ireland Ltd. All rights reserved.