The effects of sodium nitroprusside (SNP) on intestinal electrolyte transport were studied in rat colon mounted in Ussing chambers. Serosal addition of SNP increases short-circuit current (Isc) in a concentration-dependent manner. The maximal change in Isc was 35.6 +/- 2.3 microA/cm2 at 1 mM SNP (ED50 approximately 81 microM). S-nitroso-N-acetylpenicillamine, a nitrosothiol which can release nitric oxide, also stimulated an increase in Isc of 13.9 +/- 3.1 microA/cm2 at a concentration of 100 microM. The response to SNP was rapid, peaking at about 4 min with partial return to baseline at 20 to 30 min. Isc responses to SNP were significantly less in the cecum and ileum as well as after mucosal addition in the distal colon. Pretreatment with serosal atropine, cimetidine, pyrilamine, ketanserin, and N omega-nitro-L-arginine and mucosal amiloride did not inhibit the SNP-stimulated Isc; iodine, methylene blue, bumetanide, piroxicam, and tetrodotoxin each significantly decreased the response and piroxicam plus tetrodotoxin abolished it. Transmural 22Na+ and 36Cl- flux studies demonstrated that the change in Isc produced by SNP was attributable to anion secretion. SNP also inhibited neutral Na+ and Cl- absorption, with the inhibition of Na+, but not Cl- absorption eliminated by tetrodotoxin and piroxicam pretreatment. In summary, SNP has several effects on intestinal electrolyte transport, suggesting that nitric oxide or other components of nitrovasodilators may be important physiological mediators of salt and water transport and may play a role in stimulated colonic epithelial electrolyte transport in inflamed tissues.