Involvement of cyclic GMP-dependent mechanism in the nitrergic relaxation of the bovine oesophageal groove

1 The present study was designed to investigate the mechanisms involved in the relaxations to nitric oxide (NO) of bovine oesophageal groove preparations suspended in organ baths for isometric tension recordings. In preparations treated with guanethidine (10(-5) M) and atropine (10(-7) M) to block adrenergic neurotransmission and muscarinic receptors, respectively, NO released from nitrergic nerves by electrical field stimulation (EFS, 0.5-16 Hz, 1 ms duration, 20 s trains) and exogenously applied as an acidified solution of sodium nitrite (NaNO2, 10(-6)-10(-3) M) caused frequency-and dose-dependent relaxations of noradrenaline (NA, 10(-5) M)-precontracted preparations. 2 Incubation with an inhibitor of NO-stimulated soluble guanylate cyclase, 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, 3 x 10(-6) M, for 30 min) did not change the basal tension of oesophageal groove strips but inhibited relaxations to EFS and to exogenous NO. 3 Treatment with iberiotoxin (10(-7) M) and apamin (5 x 10(-7) M), which are blockers of large and small conductance Ca2+-activated K+ channels, respectively, did not modify basal tension or the relaxations induced by EFS and exogenous NO. Incubation with iberiotoxin (10(-7) M) or apamin (5 x 10(-7) M) plus ODQ (3 x 10(-6) M) significantly reduced the relaxations to EFS and exogenous NO. However, in both cases the reductions were similar to the inhibition caused by ODQ alone. The combined addition of charybdotoxin (3 x 10(-8) M) and apamin (5 x 10(-7) M) did not change relaxations to EFS or exogenous NO of the bovine oesophageal groove. 4 The blocker of ATP-sensitive K+ channels, glibenclamide (10(-6) M), had no effect on either resting tension or relaxations induced by both EFS and exogenous NO. Combined treatment with ODQ (3 x 10(-6) M) and glibenclamide (10(-6) M) did not produce additional inhibition compared to ODQ alone. 5 The present results indicate that NO acts as an inhibitory neurotransmitter by relaxing bovine oesophageal groove smooth muscle through a guanylate cyclase-dependent mechanism which does not appear to involve the opening of K+ channels.