Myogenic NOS and endogenous NO production are defective in colon from dystrophic (mdx) mice

The aim of the present study was to evaluate whether alterations in the dis tribution and/or function of nitric oxide synthase (NOS) could be involved in the development of the spontaneous mechanical tone observed in colon fro m dystrophic (mdx) mice. By recording the intraluminal pressure of isolated colon from normal mice, we showed that N-omega-nitro-L- arginine methyl es ter (L-NAME) increased the tone, even in the presence of tetrodotoxin. The effect was prevented by L-arginine, nifedipine, or Ca2+-free solution. In c olon from mdx mice, L-NAME was ineffective. Immunohistochemistry revealed t hat the presence and distribution of neuronal (nNOS), endothelial, and indu cible NOS isoforms in smooth muscle cells and neurons of colon from mdx mic e were the same as in controls. However, the expression of myogenic nNOS wa s markedly reduced in mdx mice. We conclude that there is a myogenic NOS in mouse colon that can tonically produce nitric oxide to limit influx of Ca2 + through L-type voltage-dependent channels and modulate the mechanical ton e. This mechanism appears to be defective in mdx mice.