Constitutive nitric oxide release modulates neurally-evoked chloride secretion in guinea pig colon

The role of constitutive nitric oxide (NO) release in enteric neural pathwa ys regulating ion transport was examined in guinea pig distal colon, in vit ro and ex vivo. In in vitro studies, 43% of colonic preparations exhibited oscillations in baseline short-circuit current (I-sc), which were reduced b y tetrodotoxin (TTX). The NO chelator, hemoglobin (Hb). and neuronal NO syn thase inhibitor, 7-nitroindazole (7-NI), significantly increased the baseli ne I-sc in these tissues, which was reduced by TTX. In tissues without osci llations in baseline I-sc, Hb reduced the I-sc, while 7-NI had little effec t. In all tissues, electrical held stimulation (EFS; 15 V/10 Hz) caused a b iphasic increase in the I-sc, which was enhanced by both Hb and 7-NI. In th e ex vivo studies, basal release of nitric oxide was significantly lower in colonic segments isolated from guinea pigs administered N-omega-nitro-L-ar ginine methyl ester (L-NAME) i.p. compared to control tissues. Moreover. ca rbachol, caused a 10-fold increase in NO release in control tissues, but ha d no effect in tissues isolated from the L-NAME group. L-NAME increased tis sue conductance and EFS-induced changes in I-sc, which were reversed by L-a rginine. However, carbachol-induced ion secretion was unaltered in the L-NA ME group compared to control animals. The results suggest that, in guinea p ig colon, constitutive enteric NO release tonically suppresses submucous ne ural activity and it is involved in the maintenance of basal epithelial chl oride secretion and mucosal permeability. Hence, constitutive NO promotes a delicate balance between pro-absorptive and pro-secretory processes in gui nea pig colon. (C) 2000 Elsevier Science B.V. All rights reserved.