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

Abstract

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.

Effect of sildenafil, a phosphodiesterase‐5 inhibitor, on oesophageal peristalsis and lower oesophageal sphincter function in cats

“…The inhibitory pathway of the oesophagus involves the synthesis and release of NO by central neurones within the vagal nuclei in the brain stem and peripheral neurones in the myenteric plexus 2 . The effect of NO is mediated by cGMP 11–16 . In this study we investigated the effect of sildenafil, a drug that increases intracellular cGMP, on oesophageal motor function.…”

“…In the oesophagus, NO provokes hyperpolarization of the circular smooth muscle, which regulates the progression of peristaltic contractions 3–6 and relaxes the LOS 7–10 . The effect of nitric oxide is mediated by an increase in content of cyclic guanine monophosphate (cGMP), an intracellular messenger that relaxes smooth muscle 11–16 . Cyclic GMP is broken down rapidly by phosphodiesterase‐5.…”

Gastrointestinal Function Regulation by Nitrergic Efferent Nerves

“…Thus, the authors concluded that nNOS rather than eNOS is the enzymatic source of NO. Cyclic GMP is involved in the NO-mediated relaxation in canine (Daniel et al, 2002) and bovine LES (Barahona et al, 1999). Histological studies have demonstrated the presence of neurons containing nNOS or NADPH diaphorase and costaining for VIP and galanin in the human (Singaram et al, 1994), cat (Ny et al, 1995), monkey (Rodrigo et al, 1998), guinea pig (Morikawa and Komuro, 1998), bovine (Vittoria et al, 2000), and porcine esophagus (Wu et al, 2003).…”