| Abstract: | The role of nitric oxide in intestinal fluid andelectrolyte secretion depends upon whether theconditions under study are physiological orpathophysiological. In physiological conditions,endogenous nitric oxide seems to be a proabsorptive molecule,based on the findings that nitric oxide synthaseinhibitors reverse net fluid absorption to net secretionin mice, rats, guinea pigs, rabbits, and dogs. This proabsorptive mode involves the enteric nervoussystem, the suppression of prostaglandin formation, andthe opening of basolateral K+ channels.However, in some pathophysiological states nitric oxidesynthase may be produced at higher concentrations thatare capable of evoking net secretion. Thus nitric oxidesynthase contributes to the diarrheal response intrinitrobenzene sulfonic acid-induced ileitis in guinea pigs and is the mediator of the laxative actionof several intestinal secretagogues including castoroil, phenolphthalein, bisacodyl, magnesium sulfate, bilesalts, senna, and cascara in the rat. Corresponding with the in vivo results, nitric oxide-donatingcompounds or nitric oxide itself stimulate chloridesecretion in the guinea pig and rat intestine in vitro.Exceptions are the diarrhea produced by bacterial enterotoxins in the rat, in which nitric oxideseems to have a proabsorptive role, and the mouse ileumin vitro, in which nitric oxide-donating compoundsproduce a net proabsorptive effect on basal ion transport. Several endogenous secretagogues(substance P, 5-hydroxytryptamine, interleukin-1beta),which are important mediators of the inflammatory boweldiseases, act, at least in part, through the liberation of nitric oxide. Clinical studies have shownthat nitric oxide is elevated in several inflammatorybowel diseases and other secretory conditions includingulcerative colitis, Crohn's disease, toxic megacolon, diverticulitis, infectious gastroenteritis, andinfantile methemoglobinemia. However, the determinationof nitric oxide in secretory diarrhea per se does notgive conclusive information on the nitric oxide contribution to clinical secretorydiarrhea. |
