Influence of nitric oxide and vasoactive intestinal peptide on the spontaneous and triggered electrical and mechanical activities of the canine ileum
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abstract
Modulation of canine ileal pacemaker activity by nitric oxide (NO) or vasoactive intestinal peptide (VIP) was studied during recording of the intracellular electrical and mechanical activity from the entire muscularis externa and from an isolated circular muscle preparation both cut in the long axis of the circular muscle. In the whole-thickness preparation with cholinergic and adrenergic nerve function blocked, the inhibitory junction potentials (IJPs) recorded near the myenteric plexus (MyP) or deep muscular plexus (DMP) were abolished by omega-conotoxin GVIA (omega-CTX, 10(-7) to 3 x 10(-7) M), tetrodotoxin (TTX, 1 microM), or the NO synthase (NOS) inhibitor N omega-nitro-L-arginine (L-NNA at 50 microM). IJPs from electrical field stimulation triggered slow waves (TSWs); after TTX or omega-CTX, TSWs still occurred, advanced in time 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 waves, or TSWs evoked by a long stimulating pulse unchanged. L-NNA at 100 microM enhanced the amplitude but not the frequency of spontaneous slow waves. TTX and NOS blockers all increased circular muscle contractions associated with the spontaneous slow waves and TSWs. In isolated circular muscle preparations, the NOS inhibitors N omega-nitro-L-arginine methyl ester (L-NAME at 300 microM) or L-NNA at 100 microM abolished the 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 hydrochloride (SIN-1) at 200 microM caused hyperpolarizations (10-15 mV) similar to the IJP mediator, attenuated the IJPs, and abolished mechanical activities. SIN-1 increased the slow wave frequency but decreased the amplitude and duration of spontaneous slow waves and TSWs. VIP (10(-6) M) decreased contraction and slow wave amplitude and prolonged IJP duration 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 inputs that release NO to mediate IJPs and relaxation and influence the delay before a TSW. NO (not VIP) release from nerves inhibits initiation of spontaneous slow waves or TSWs near the MyP, and spontaneous NO release modulates pacemaking activity from the DMP.
