Article date: September 1991
By: A. Tøttrup, M.A. Knudsen, H. Gregersen, in Volume 104, Issue 1, pages 113-116
The role of the l‐arginine‐nitric oxide pathway in lower oesophageal sphincter (LOS) relaxation and oesophageal peristalsis was investigated.
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.
Nω‐nitro‐l‐arginine (l‐NNA, 10−8–10−5mol 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, (10−5mol kg−1) was fully reversed by infusion of 10−4mol kg−1l‐arginine. Peristaltic velocity and amplitude of contractions in the oesophageal body were unaffected by l‐NNA.
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.
A significant elevation of blood pressure was recorded after administration of l‐NNA (10−5mol kg−1).
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.
The role of the l‐arginine‐nitric oxide pathway in lower oesophageal sphincter (LOS) relaxation and oesophageal peristalsis was investigated.
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.
Nω‐nitro‐l‐arginine (l‐NNA, 10−8–10−5mol 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, (10−5mol kg−1) was fully reversed by infusion of 10−4mol kg−1l‐arginine. Peristaltic velocity and amplitude of contractions in the oesophageal body were unaffected by l‐NNA.
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.
A significant elevation of blood pressure was recorded after administration of l‐NNA (10−5mol kg−1).
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.
DOI: 10.1111/j.1476-5381.1991.tb12393.x
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