ROLE OF NITRIC OXIDE-RELATED INHIBITION IN INTESTINAL FUNCTION - RELATION TO VASOACTIVE INTESTINAL POLYPEPTIDE

Role of nitric oxide-related inhibition in intestinal function: relati on to vasoactive intestinal polypeptide. Am. J. Physiol. 266 (Gastroin test. Liver Physiol. 29): G31-G39, 1994.-This study examined the role of nitric oxide (NO) in tonic inhibition of motor activity in isolated , perfused canine ileal segments. Brief addition of N omega-nitro-L-ar ginine methyl ester (L-NAME) to the perfusate caused, after a delay, a concentration-dependent persistent increase in tonic and phasic activ ity of circular muscle. This increased motor activity was prevented or reversed by addition of L- but not D-arginine to the perfusate. Remov al of Ca2+ or addition of 10(-7) M omega-conotoxin (GVIA) to the perfu sate markedly reduced this response. The motor activity induced by L-N AME was accompanied by loss of distal inhibition and enhanced excitati on to low-frequency field stimulation. L-NAME infusion significantly r educed tonic vasoactive intestinal polypeptide (VIP) output, sodium ni troprusside increased VIP output, but L-arginine infusion did not rest ore VIP output. Atropine (10(-7) M) and/or hexamethonium (10(-4) M) re duced the motor response to L-NAME by 75%. Atropine reduced and hexame thonium nearly abolished VIP output. We conclude that there is tonic C a2+-dependent NO output from perfused intestinal segments dependent on nerves with N-Ca channels, that NO acts to inhibit muscle directly an d by inhibiting release of excitatory mediators, and that this output is the primary inhibitory determinant of contractile activity.