Nitric oxide affects mammalian distal colonic smooth muscle by tonic neural inhibition.
1 The role of the L-arginine-nitric oxide (NO) pathway in tonic neural inhibition of spontaneous mechanical activity of distal colonic circular smooth muscle (DCCSM) was investigated in male Wistar rats. 2 Muscle strips were mounted in organ baths and spontaneous contractions recorded with isometric force transducers. They were characterized as low frequency (LFCs) 0.41 +/- 0.03 N cm-2 or high frequency contractions (HFCs) 0.22 +/- 0.04 N cm-2. The latter occurred intermittently to produce summation contractions (SCs) range 0.5-12 N cm-2. 3 Tetrodotoxin (100 nM) increased the forces of LFCs and SCs. Increase in force to tetrodotoxin did not occur after incubation of the muscle with NG-monomethyl-L-arginine (L-NMMA) 500 microM, an inhibitor of NO biosynthesis. 4 L-NMMA but not its enantiomer D-NMMA increased the force of LFCs (EC50: 200 microM) and SCS (EC50:175 microM) in a concentration-dependent manner which was reversed by L-arginine but not by D-arginine. 5 Muscle, precontracted by acetylcholine, relaxed to sodium nitroprusside (EC50:1.8 microM) NO gas (EV50:70 microliters) and NO solutions (EC50:4 microM) in a concentration-dependent manner. Guanosine 3':5'-cyclic monophosphate tissue concentrations (pmol mg-1 protein) were elevated in muscle after relaxation by sodium nitroprusside (500 microM) from 0.32 +/- 0.06 to 1.2 +/- 0.37 and by 1 ml of NO gas from 0.49 +/- 0.05 to 1.54 +/- 0.14. 6 These data suggest that DCCSM is under tonic neural inhibition mediated by NO biosynthesis.
Department of Gastroenterology, Addenbrooke's Hospital, Cambridge.
S J
SJ
Middleton
A W
AW
Cuthbert
M
M
Shorthouse
J O
JO
Hunter
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D003106:Colon / Q000187:drug effects / Q000294:innervation*; D006152:Cyclic GMP / Q000378:metabolism; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009433:Neural Inhibition / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology*; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D013779:Tetrodotoxin / Q000494:pharmacology; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D013779:Tetrodotoxin; D001120:Arginine; D006152:Cyclic GMP; D000109:Acetylcholine