Mechanism of nitric oxide‐induced contraction in the rat isolated small intestine

The contractile response to nitric oxide (NO) in ral ileal myenteric plexus‐longitudinal muscle strips was pharmacologically analysed. NO (10 −7 m ) induced only contraction while 10 −6 m NO induced contraction followed by relaxation. Methylene blue (up to 10 −4 m ) did not affect the NO‐induced contractions but significantly reduced the relaxation evoked by 10 −6 m NO. Administration of 8‐bromo‐cyclic GMP (10 −6 –10 −4 m ) only induced relaxation. Sodium nitroprusside (SNP; 10 −7 –10 −5 m ) induced concentration‐dependent contractions per se ; the contractile response to NO, administered within 10 min after SNP, was concentration‐dependently reduced. The guanosine 3′:5′‐cyclic monophosphate (cyclic GMP) content of the tissues was not increased during contractions with 10 −8 m NO and 10 −6 m SNP; it was increased by a factor of 2 during contraction with 10 −7 m NO, and by a factor of 12 during relaxation with 3×10 −6 m NO. The NO‐induced contractions were not affected by ryanodine (3×10 −5 m ) but were concentration‐dependently reduced by nifedipine (10 −8 –10 −7 m ) and apamin (3×10 −9 –3×10 −8 m ). These results suggest that cyclic GMP is not involved in the NO‐induced contraction in the rat small intestine. The NO‐induced contraction is related to extracellular Ca 2+ influx through L‐type Ca 2+ channels, that might be activated in response to the closure of Ca 2+ ‐dependent K + channels.British Journal of Pharmacology (1997) 120 , 975–981; doi: 10.1038/sj.bjp.0700996