Evidence for a role for nitric oxide in relaxation of the frog oesophageal body to electrical field stimulation

1 Electrical field stimulation (EFS) (1–10 Hz, 30 V, 2 ms) of frog oesophageal body strips resulted in frequency‐dependent non‐adrenergic, non‐cholinergic (NANC) relaxations. 2 Tetrodotoxin (TTX) (10 −6 –10 −5   M ) had no effect on EFS evoked relaxations with a 2 ms pulse width. At a pulse width of 0.5 ms only the responses to the highest frequency (10 Hz) were significantly inhibited by TTX at 10 −5   M . Relaxations at the 2 ms pulse width were unaffected by ω‐conotoxin (10 −6   M ), nifedipine (10 −6   M ) or cobalt (5×10 −4   M ). 3 N G ‐nitro‐ L ‐arginine ( L ‐NOARG) (10 −6 –10 −4   M ), a nitric oxide synthase (NOS) inhibitor, caused a concentration‐dependent inhibition of the EFS‐induced NANC relaxant responses. The inhibitory effect of L ‐NOARG was both prevented and reversed by L ‐arginine but not D ‐arginine (5×10 −3   M ). 4 The phosphodiesterase type V inhibitor (PDE V), SK&F 96231 (10 −7 –10 −4   M ), caused a concentration‐dependent potentiation of both the percentage relaxation and the duration of the relaxant responses to EFS. 5 ODQ (10 −7 –10 −5   M ), a guanylate cyclase inhibitor, produced a concentration‐dependent inhibition of EFS‐evoked NANC relaxations. 6 Oxyhaemoglobin (10 −6   M ), which binds nitric oxide (NO), inhibited NANC relaxations to EFS. 7 The NO donor sodium nitroprusside (SNP) (10 −8 –10 −4   M ) produced a concentration‐dependent inhibition of evoked tone. L ‐NOARG (10 −4   M ) had no effect on the SNP evoked relaxations. Preincubation with oxyhaemoglobin (10 −6   M ) caused a reduction in the SNP (10 −6 –10 −5   M ) induced relaxations. 8 These results suggest NO is the relaxant transmitter of the frog oesophageal body and the source of NO may be non‐neuronal.British Journal of Pharmacology (1997) 122 , 179–185; doi: 10.1038/sj.bjp.0701298