THE ROLE OF THE L-ARGININE-NITRIC OXIDE PATHWAY IN RELAXATION OF THE OPOSSUM LOWER ESOPHAGEAL SPHINCTER

1 The role of the L-arginine-nitric oxide pathway in lower oesophageal sphincter (LOS) relaxation and oesophageal peristalsis was investigated. 2 Twenty four adult opossums were anaesthetized and the right vagus nerve was isolated in the neck and sectioned. Electrical stimulation, applied to the peripheral end of the nerve, resulted in a frequency-dependent relaxation of the LOS, and peristaltic and non-peristaltic contractions in the oesophageal body. 3 N-omega-nitro-L-arginine (L-NNA, 10(-8)-10(-5) mol kg-1), an inhibitor of the L-arginine-nitric oxide pathway, inhibited LOS relaxation in a dose-dependent manner, but did not affect resting LOS pressure. At the highest dose of L-NNA no relaxation of the LOS was elicited in response to vagal stimulation. The effect of L-NNA, (10(-5) mol kg-1) was fully reversed by infusion 10(-4) mol kg-1 L-arginine. Peristalitic velocity and amplitude of contractions in the oesophageal body were unaffected by L-NNA. 4 Infusion of sodium nitroprusside reduced LOS pressure to zero, and the drug was equally potent in control animals (- log ED50 : 8.1 +/- 0.2 mol kg-1) and in animals pretreated with L-NNA (- log ED50: 8.2 +/- 0.3 mol kg-1). This suggests that the effect of L-NNA was not directly on guanylate cyclase. 5 A significant elevation of blood pressure was recorded after administration of L-NNA (10(-5) mol kg-1). 6 It is suggested that the L-arginine-nitric oxide pathway plays an important functional role for relaxation of the LOS, but not for oesophageal peristalsis. Whether the active substance is nitric oxide or a related nitroso-compound remains to be settled.