Sodium nitrite, a potent relaxant of rat stomach fundus: in vitro evidence

The effects of sodium nitrite (0.1, 1, 10 mM) on mechanical activity of iso lated rat stomach fundus muscle and the influence of guanylate cyclase acti vity inhibitor (methylene blue) and channel inhibitors (tetrodotoxin, chary bdotoxin, apamin) were studied. Nitrite evoked dose-dependent relaxation in the longitudinal and circular muscle layers. The lowest effective concentr ation of sodium nitrite was 0.1 mM, which is comparable with the NOAEL (no observed adverse effect level). Tetrodotoxin (1 mu M) markedly inhibited el ectrically induced contraction and rebound relaxation, but did not influenc e the nitrite-induced relaxation. Charybdotoxin (100 nM) decreased the rela xation evoked by 10 mM nitrite to 52.3 and 65.7% of control reaction in the circular and longitudinal muscle layer, respectively. Apamin (100 nM) did not influence the nitrite-induced relaxation. Methylene blue (10 mu M) decr eased relaxation induced by nitrite in the longitudinal and circular muscle layer, respectively to 66.7 and 54.3% of the response to 1 mM nitrite alon e. Relaxation induced by nitrite was decreased in the presence of L-cystein e (5 mM), and in the circular and longitudinal muscle layer reached 29.6 an d 23.1%, respectively, of the response to 1 mM nitrite alone. We conclude t hat the relaxing effect of nitrite on gastric fundus results from its direc t action on smooth muscle cells and probably the enteric nervous system is not involved in this action. The nitrite-elicited relaxation depends on act ivation of guanylate cyclase and high conductance Ca2+-activated potassium channels; however, activation of potassium channels might be a part of or m ight act in parallel with the mechanism involving the cyclic GMP system. Ef fects of nitrite observed in the presence of L-cysteine suggest that nitros othiols are not responsible for nitrite-evoked activation of guanylate cycl ase.