Nitric oxide production is diminished in colonic circular muscle from acquired megacolon

PURPOSE: Nitric oxide modulates human colonic smooth muscle function. To determine whether nitric oxide production is altered in colon from acquired megacolon, we measured cholinergic nerve-mediated contractions in vitro before and after inhibition of nitric oxide synthase. METHODS: Intramural nerves in circular smooth muscle from histologically normal colon (n = 12) and acquired megacolon (n = 3) were activated by electrical field stimulation. RESULTS: In controls blockade of nitric oxide synthase by N-G-Nitro-L-Arginine induced increases (P <0.05) in amplitude of contractions; these increases in amplitudes were blocked by L-Arginine (analysis of variance; P < 0.05). By contrast, blockade of nitric oxide synthase did not increase amplitudes of contractions with circular smooth muscle from acquired megacolon. An immediate phasic contraction was blocked by atropine sulfate. CONCLUSIONS: The results support the concept that nitric oxide production modulates cholinergic nerve-mediated contractions in normal colonic circular muscle, whereas acquired megacolon is associated with altered release of this inhibitory neurochemical. Potential explanations include depletion of tissue L-Arginine, decreased capacity to recycle citrulline to arginine, or decreased release of vasoactive intestinal peptide from circular smooth muscle in acquired megacolon.