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 N((G)monomethyl-L-arginine (L-NMMA) 500 mum, an inhibitor of NO biosynthesis. 4 L-NMMA but not its enantiomer D-NMMA increased the force of LFCs (EC50:200 mum) and SCs (EC50:175 mum) 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 mum) NO gas (EV50:70 mul) and NO solutions (EC50:4 mum) 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 mum) 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.