NANC relaxation of the circular smooth muscle of the oesophagus of the Agama lizard involves the l-arginine–nitric oxide synthase pathway

Abstract

On carbachol (CCh; 10–30 μM) pre-contracted circular muscle strips of the Agama lizard oesophagus, electrical field stimulation evoked frequency-dependent relaxations in the presence of guanethidine (1 μM) and indomethacin (1 μM). These non-adrenergic inhibitory responses were concentration-dependently inhibited by the nitric oxide synthase (NOS) inhibitor N ω -nitro- l-arginine methyl ester ( l-NAME) within a concentration range of 30–300 μM but not d-NAME (up to 300 μM), although a component remained at 4–16 Hz even with 300 μM l-NAME. The inhibition by l-NAME (300 μM) was completely prevented when l-arginine ( l-Arg; 15 mM) but not d-Arg (up to 15 mM) was applied simultaneously with l-NAME (300 μM). Increasing the l-NAME concentration to 1 mM had no additional inhibitory effect. Sodium nitroprusside (SNP) concentration-dependently relaxed pre-contracted oesophageal strips, l-NAME (up to 300 μM) had no effect. Neither adenosine 5′-triphosphate (up to 0.1 mM) nor vasoactive intestinal polypeptide (up to 0.1 μM) caused the pre-contracted oesophagus to relax. This study has shown that the NANC inhibitory response of the Agama lizard oesophagus circular muscle largely involves the l-Arg-NOS pathway as seen by the effect of l-NAME, l-Arg and SNP. The identity of the l-NAME-resistant component(s) and the lack of effect of tetrodotoxin (up to 3 μM) and ω-conotoxin GVIA (up to 0.1 μM) in relation to the nature of the inhibitory response are discussed.