Nitric oxide-mediated contraction in enteric smooth muscle

Abstract

Nitric oxide (NO) seems to be involved as neurotransmitter in nonadrenergic noncholinergic (NANC) smooth muscle relaxation throughout the gastrointestinal tract. Contractile responses to NO in the gastrointestinal smooth muscle have also been reported. In the guinea-pig ileal longitudinal muscle-myenteric plexus preparation at basal tone, NO induces a moderate relaxation followed by an aftercontraction; the latter is blocked by tetrodotoxin. The aftercontraction is also reduced by atropine, the remaining part being inhibited by a substance P antagonist. This indicates the activation of cholinergic and, possibly, tachykininergic neurons; it is not clear whether this represents a rebound phenomenon to the relaxation or a direct action of NO, initially masked by the relaxation. Nitrergic "off"-contractions, in response to electrical stimulation of the inhibitory NANC nerves, were reported in the opossum esophageal body and in the cat distal colon. Primary contractions to NO have been reported in the rat ileum and in the longitudinal muscle of the opossum esophagus. In the rat preparation, the contraction to NO is observed at lower concentrations than the relaxant effect. While the contraction in the opossum seems to be related to guanylate cyclase activation, this is not the case in the rat ileum, as methylene blue did not influence the contractions and 8-bromo-cGMP only had a relaxant effect. No clear-cut rise in cGMP was observed during the NO-induced contraction. The NO-induced contraction was also not influenced by ryanodine but it was concentration-dependently reduced by nifedipine, suggesting that it is related to extracellular calcium influx through L-type calcium channels. Primary contractions due to NO were also observed in the rat whole ileum and in the rat caecal longitudinal muscle, while aftercontractions, due to NO, were also obtained in the rat descending, transverse and sigmoid colon, as well as in the cat ileal longitudinal muscle.