MECHANISM OF NITRIC OXIDE-INDUCED CONTRACTION IN THE RAT ISOLATED SMALL-INTESTINE

1 The contractile response to nitric oxide (NO) in ral ileal myenteric plexus-longitudinal muscle strips was pharmacologically analysed. 2 N O (10(-7) M) induced only contraction while 10(-6) M NO induced contra ction followed by relaxation. Methylene blue (up to 10(-4) M) did not affect the NO-induced contractions but significantly reduced the relax ation evoked by 10(-6) M NO. Administration of 8-bromo-cyclic GMP (10( -6)-10(-4) M) only induced relaxation. 3 Sodium nitroprusside (SNP; 10 (-7)-10(-5) M) induced concentration-dependent contractions per se; th e contractile response to NO, administered within 10 min after SNP, wa s concentration-dependently reduced. The guanosine 3':5'-cyclic monoph osphate (cyclic GMP) content of the tissues was not increased during c ontractions with 10(-8) M NO and 10(-6) M SNP; it was increased by a f actor of 2 during contraction with 10(-7) M NO, and by a factor of 12 during relaxation with 3 x 10(-6) M NO. 4 The NO-induced contractions were not affected by ryanodine (3 x 10(-5) M) but were concentration-d ependently reduced by nifedipine (10(-8)-10(-7) M) and apamin (3 x 10( -9)-3 x 10(-8) M). 5 These results suggest that cyclic GMP is not invo lved in the NO-induced contraction in the rat small intestine. The NO- induced contraction is related to extracellular Ca2+ influx through L- type Ca2+ channels, that might be activated in response to the closure of Ca2+-dependent K+ channels.