INFLUENCE OF NITRIC-OXIDE AND VASOACTIVE-INTESTINAL-PEPTIDE ON THE SPONTANEOUS AND TRIGGERED ELECTRICAL AND MECHANICAL ACTIVITIES OF THE CANINE ILEUM

Modulation of canine ileal pacemaker activity by nitric oxide (NO) or vasoactive intestinal peptide (VIP) was studied during recording of th e intracellular electrical and mechanical activity from the entire mus cularis externa and from an isolated circular muscle preparation both cut in the long axis of he circular muscle. In the whole-thickness pre paration with cholinergic and adrenergic nerve function blocked, the i nhibitory junction potentials (IJPs) recorded near the myenteric plexu s (MyP) or deep muscular plexus (DMP) were abolished by omega-conotoxi n GVIA (omega-CTX, 10(-7) to 3 x 10(-7) M), tetrodotoxin (TTX, 1 mu M) , or the NO synthase (NOS) inhibitor N-omega-nitro-L-arginine (L-NNA a t 50 mu M). IJPs from electrical field stimulation triggered slow wave s (TSWs); after TTX or omega-CTX, TSWs still occurred, advanced in tim e and increased in amplitude after TTX. Addition of L-NNA advanced the onset of the TSWs after omega-CTX. TTX, L-NNA, or omega-CTX left the resting membrane potentials, the characteristics of spontaneous slow w aves, or TSWs evoked by a long stimulating pulse unchanged. L-NNA at 1 00 mu M enhanced the amplitude but not the frequency of spontaneous sl ow waves. TTX and NOS blockers all increased circular muscle contracti ons associated with the spontaneous slow waves and TSWs. In isolated c ircular muscle preparations, the NOS inhibitors N-omega-nitro-L-argini ne methyl ester (L-NAME at 300 mu M) or L-NNA at 100 mu M abolished th e IJPs and increased the regularity and amplitude of spontaneous slow waves and associated contractions, but TSWs could not be evoked before or after NOS inhibition. The NO donor 3-morpholinosydnonimine hydroch loride (SIN-1) at 200 mu M caused hyperpolarizations (10-15 mV) simila r to the IJP mediator, attenuated the IJPs, and abolished mechanical a ctivities. SIN-1 increased the slow wave frequency but decreased the a mplitude and duration of spontaneous slow waves and TSWs. VIP (10(-6) M) decreased contraction and slow wave amplitude and prolonged LTP dur ation without affecting membrane potential or slow wave frequency. We conclude that spontaneous slow waves and TSWs originate independently of neural activity. Pacemaking regions possess inhibitory neural input s that release NO to mediate IJPs and relaxation and influence the del ay before a TSW. NO (not VIP) release from nerves inhibits initiation of spontaneous slow waves or TSWs near the MyP, and spontaneous NO rel ease modulates pacemaking activity from the DMP.