Nitrergic regulation of colonic transit in rats

Nitric oxide has been shown to be an inhibitory neurotransmitter in the mammalian colon, although its role in colonic transit remains unclear. We investigated the effect of the nitric oxide biosynthesis inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) on colonic transit in conscious rats. Colonic transit was determined by calculating the geometric center of the distribution of radiochromium instilled into the proximal colon. We also studied the effect of L-NAME on colonic motility in vivo and on descending relaxation in vitro. L-NAME (10 mg/kg) significantly delayed colonic transit compared with saline. The inhibitory effect of L-NAME was prevented by L-arginine (100 mg/kg) but not by D-arginine (100 mg/kg). L-NAME (10 mg/kg) induced random and uncoordinated phasic contractions throughout the rat colon in vivo. Luminal distension evoked descending relaxation in the proximal and distal rat colon in vitro. L-NAME (10(-4) M) significantly inhibited this relaxation. It is suggested, therefore, that nitric oxide enhances transit in the rat colon by mediating descending relaxation, which, in turn, facilitates propulsion of the colonic contents.