Differential effect of nitric oxide synthase inhibition on sigmoid colon longitudinal and circular muscle responses to nicotine and nerve stimulation in vitro.
BACKGROUND
Nicotine has been shown to release nitric oxide from nerves in human sigmoid colon. This effect has been used to investigate the innervation and functional relationship of the longitudinal and circular muscle layers.


METHODS
Strips of longitudinal and circular muscle were obtained from 19 patients with colorectal cancer. The strips from ten patients were subjected to electrical field stimulation (EFS) in vitro using stimulus parameters for selective stimulation of nerves. The effect of nicotine 1-10 micromol/l on EFS responses was then measured in the presence and absence of a nitric oxide synthase inhibitor, nitro-L-arginine methyl ester (L-NAME) 200 micromol/l. The effect of nicotine on spontaneous activity was investigated in the muscle strips from the other nine patients.


RESULTS
Both longitudinal and circular strips responded to EFS with contraction. The time to achieve a peak contractile response (time to peak; TTP) was significantly longer (P<0.001) in circular strips. L-NAME reduced the mean(s.e.m.) TTP in circular muscle from 23.3(2.0) to 17.2(1.5) s (P=0.007) and altered its pattern of response to resemble that of longitudinal muscle. Nicotine 10 micromol/l reduced the contraction to EFS in circular (P<0.001) but not in longitudinal (P=0.347) muscle. The nicotine-induced reduction in circular muscle contraction was blocked by L-NAME 200 micromol/l (P=0.005).


CONCLUSIONS
These findings suggest that nitric oxide release on neural stimulation is greater in circular than in longitudinal muscle.
McKirdy
H C
HC
Department of Surgery, University of Wales College of Medicine, Cardiff, UK.
Richardson
C E
CE
Green
J T
JT
Rhodes
J
J
Williams
G T
GT
Marshall
R W
RW
D012809:Colon, Sigmoid / Q000187:drug effects* / Q000201:enzymology; D015179:Colorectal Neoplasms / Q000503:physiopathology; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005731:Ganglionic Stimulants / Q000494:pharmacology*; D006801:Humans; D009119:Muscle Contraction / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D005731:Ganglionic Stimulants; D018722:Nicotinic Agonists; D009538:Nicotine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester