Nitric oxide as a mediator of the laxative action of magnesium sulphate.

1. Magnesium sulphate was studied for its effects on diarrhoea, fluid secretion, gastrointestinal transit and nitric oxide (NO) synthase activity in rats. 2. At a dose of 2 g kg-1 orally magnesium sulphate produced diarrhoea that was delayed in onset and intensity in a dose-related manner by the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). This was prevented by the NO precursor, L-arginine and the NO donating compound, isosorbide-5-mononitrate (IMN). 3. Nitric oxide synthase activity was stimulated in gut tissue from rats given magnesium sulphate and this was inhibited by L-NAME. Dexamethasone (1 mg kg-1, i.p.), an inhibitor of inducible NO synthase, had no effect on magnesium sulphate-induced diarrhoea. 4. Magnesium sulphate stimulated fluid and electrolyte accumulation in the intestinal lumen; these effects were prevented by L-NAME but not D-NAME. 5. Gastrointestinal transit of a non-absorbable marker (charcoal suspension) was increased by oral magnesium sulphate from a mean value of 54.1% to 72.9% (P < 0.01), and this was prevented by pretreatment with L-NAME. 6. The results demonstrate that oral magnesium sulphate produces diarrhoea in rats by increasing the accumulation of fluid in the intestinal lumen and enhancing flow from the proximal to distal intestine. The mechanism involves release of NO, probably through stimulation of the constitutive form of NO synthase. Whether or not the effects of magnesium sulphate are due to an osmotic action or an intrinsic effect of the magnesium or sulphate ions cannot be determined from these experiments.