EVIDENCE FOR A ROLE FOR NITRIC-OXIDE IN RELAXATION OF THE FROG ESOPHAGEAL BODY TO ELECTRICAL-FIELD STIMULATION

1 Electrical field stimulation (EFS) (1-10 Hz, 30 V, 2 ms) of frog oes ophageal body strips resulted in frequency-dependent non-adrenergic, n on-cholinergic (NANC) relaxations. 2 Tetrodotoxin (TTX) (10(-6)-10(-5) M) had no effect on EFS evoked relaxations with a 2 ms pulse width. A t 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 a t the 2 ms pulse width were unaffected by omega-conotoxin (10(-6) M), nifedipine (10(-6) M) or cobalt (5 x 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 r elaxant responses. The inhibitory effect of L-NOARG was both prevented and reversed by L-arginine but not D-arginine (5 x 10(-3) M). 4 The p hosphodiesterase type V inhibitor (PDE V), SK&F 96231 (10(-7)-10(-4) M ), caused concentration-dependent potentiation of both the percentage relaxation and the duration of the relaxant responses to EFS. 5 ODQ (1 0(-7)-10(-5) M), a guanylate cyclase inhibitor, produced a concentrati on-dependent inhibition of EFS-evoked NANC relaxations. 6 Oxyhaemoglob in (10(-6) M), which binds nitric oxide (NO), inhibited NANC relaxatio ns 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 relax ant transmitter of the frog oesophageal body and the source of NO may be non-neuronal.