Modulation by nitric oxide of spontaneous mechanical activity in rat proximal colon

1 In order to examine the role of nitric oxide (NO) in the tonic neural inhibition in rat proximal colon, the effects of N_ω-nitro- l -arginine methyl ester (L-NAME) were studied on the spontaneous contractions of circular muscle (monitored as intraluminal pressure changes) and of longitudinal muscle (detected as isometric tension changes). 2 L-NAME (3 × 10^??6–3 × 10^??4 m ) caused a concentration-dependent increase in the amplitude of circular contractions, without affecting those of longitudinal muscle. This effect was prevented by l -arginine (1–5 × 10^??3 m ), but not d -arginine. 3 In the presence of tetrodotoxin (10^??6 m ), which per se induced increase of the pressure waves, L-NAME (10^??4 m ) caused no further effects on the amplitude of the spontaneous contractions. 4 The response to L-NAME (10^??4 m ) was unaffected by atropine (10^??6 m ), guanethidine (10^??6 m ), hexamethonium (up to 3 × 10^??4 m ) or α-chymotrypsin (up to 5 U ml^??1). 5 NK₂ receptor antagonists, SR 48968 (3 × 10^??6 m ) or MEN 10627 (10^??6 m ), produced a reduction of the amplitude of the pressure waves but failed to affect the contractile response to L-NAME (10^??4 m ). 6 These findings suggest that tonic production of NO from inhibitory neurones influences the degree of contractions of circular muscle. An involvement of an inhibitory peptide as well as disinhibition of cholinergic or NK₂-tachykinergic excitatory neurotransmission in the mechanism of NO action can be ruled out.