BASAL RELEASE OF NITRIC-OXIDE INDUCES AN OSCILLATORY MOTOR PATTERN INCANINE COLON

1. The consequences of intrinsic, basal nitric oxide release on electr ical and contractile activity of canine proximal colon were examined. Membrane potential and contraction were simultaneously recorded from t he circular muscle in the presence of drugs to block adrenergic and ch olinergic responses. 2. Electrical slow waves were recorded from muscl e cells near the submucosal surface of the circular layer. Spontaneous contractions were initiated by each slow wave. Contractile amplitude increased 1.9-fold when nerves were blocked with tetrodotoxin (TTX, 1 mu M). 3. Muscle cells near the myenteric surface displayed myenteric potential oscillations (MPOs) averaging 16 cycles per minute (c.p.m) i n frequency and 10 mV in amplitude. Twenty-five per cent of muscles di splayed an additional slow, neurogenic oscillation (mean frequency, 1 c.p.m.; amplitude, 14 mV) superimposed upon the MPO rhythm. 4. The nit ric oxide (NO) synthase inhibitor N-omega-nitro-L-arginine (L-NA, 100 mu M; n = 16) abolished neurogenic oscillations, depolarized cells, an d increased MPO upstroke velocity, amplitude and frequency. The action s of L-NA were mimicked by N-omega-nitro-L-arginine methylester (L-NAM E, 100 mu M) and oxyhaemoglobin (3%). 5. Spontaneous contractions were increased 2.3-fold by L-NA, and TTX had no effect on contractions aft er addition of L-NA. 6. The NO-donor sodium nitroprusside (SNP, 1 mu M ) reversed the electrical and mechanical effects of L-NA and initiated slow oscillations similar to the neurogenic oscillations. Slow oscill ations were also evoked with S-nitroso-N-acetylpenicillamine (SNAP, 1 mu M). The effects of NO donors were blocked by oxyhaemoglobin. 7. Slo w electrical oscillations could not be elicited by SNP after removal o f a thin strip of circular muscle along the myenteric edge. 8. These d ata suggest that the spontaneous electrical and contractile activity o f the proximal colon is tonically suppressed by basal release of NO. B asal NO causes an oscillatory pattern of electrical and mechanical act ivity. This activity does not require patterned firing of nerves; rath er a continuous, low level release of NO would be capable of producing the neurogenic oscillatory behaviour. The slow oscillatory activity d epends upon the presence of the myenteric region of the circular muscl e layer, which contains cell bodies of enteric neurons and interstitia l cells of Cajal.