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The role of the l ‐arginine‐nitric oxide pathway in relaxation of the opossum lower oesophageal sphincter
Author(s) -
Tøttrup A.,
Knudsen M.A.,
Gregersen H.
Publication year - 1991
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1991.tb12393.x
Subject(s) - nitric oxide , opossum , sodium nitroprusside , peristalsis , stimulation , endocrinology , medicine , arginine , nitroarginine , chemistry , vagus nerve , anesthesia , nitric oxide synthase , anatomy , biochemistry , amino acid
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 ω ‐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 of 10 −4 mol kg −1 l ‐arginine. Peristaltic 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 ED 50 : 8.1 ± 0.2 mol kg −1 ) and in animals pretreated with l ‐NNA (–log ED 50 : 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.