NITRIC OXIDE-MEDIATED CONTRACTION IN ENTERIC SMOOTH-MUSCLE

Nitric oxide (NO) seems to be involved as neurotransmitter in nonadren ergic noncholinergic (NANC) smooth muscle relaxation throughout the ga strointestinal tract. Contractile responses to NO in the gastrointesti nal smooth muscle have also been reported. In the guinea-pig ileal lon gitudinal muscle-myenteric plexus preparation at basal tone, NO induce s a moderate relaxation followed by an aftercontraction; the latter is blocked by tetrodotoxin. The aftercontraction is also reduced by atro pine, the remaining part being inhibited by a substance P antagonist. This indicates the activation of cholinergic and, possibly, tachykinin ergic neurons; it is not clear whether this represents a rebound pheno menon to the relaxation or a direct action of NO, initially masked by the relaxation. Nitrergic ''off''-contractions, in response to electri cal stimulation of the inhibitory NANC nerves, were reported in the op ossum esophageal body and in the cat distal colon. Primary contraction s to NO have been reported in the rat ileum and in the longitudinal mu scle of the opossum esophagus. In the rat preparation, the contraction to NO is observed at lower concentrations than the relaxant effect. W hile the contraction in the opossum seems to be related to guanylate c yclase 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 r elaxant effect. No clear-cut rise in cGMP was observed during the NO-i nduced contraction. The NO-induced contraction was also not influenced by ryanodine but it was concentration-dependently reduced by nifedipi ne, suggesting that it is related to extracellular calcium influx thro ugh L-type calcium channels. Primary contractions due to NO were also observed in the rat whole ileum and in the rat caecal longitudinal mus cle, 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.