Background: Hyperdynamic circulation in portal hypertensive rats depends on central neural c-fos gene expression, but how the portal hypertensive signal activates central c-fos expression remains obscure.
Aim: To elucidate the afferent pathway from the gut to the central cardiovascular regulatory nuclei in portal hypertensive rats.
Methods: Cervical vagus nerves and the coeliac ganglion were treated with topical capsaicin to denervate the sensory afferents. Surgical portal vein stenosis (PVS) was performed 3 weeks after denervation. Effectiveness of vagal afferent denervation was confirmed by absent oesophagus to brainstem transfer of the neural tracer cholera toxin-conjugated horseradish peroxidase. Fos, the protein product of the c-fos gene, was detected by immunohistochemistry in central cardiovascular regulatory nuclei. Vagal nerve activity was measured after acute portal hypertension induced by an inflatable cuff around the portal vein. Cardiac output and mean arterial pressure were recorded.
Results: In vagal capsaicin-treated rats, no horseradish peroxidase was detected in the brainstem after oesophageal injection. In vagal capsaicin-treated rats subjected to PVS, Fos expression was significantly decreased in both the solitary tract nucleus and paraventricular nucleus compared with untreated PVS rats. Acute portal hypertension stimulated vagal nerve electrical activity. The hyperdynamic circulation was completely abrogated in vagal capsaicin-treated PVS rats. Capsaicin induced no neural or haemodynamic changes in either sham-operated controls or coeliac ganglion-treated PVS rats.
Conclusion: In portal hypertensive rats, central cardiovascular regulatory nuclei initiate hyperdynamic circulation in response to a gut signal associated with portal hypertension. Portal hypertension signals to the central nuclei via capsaicin-sensitive vagal afferent nerves.
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Funding: This work was supported by research operating grants from the Canadian Institutes of Health Research.
Competing interests: None.
Ethics approval: The protocol was approved by the University of Calgary Faculty of Medicine Animal Care Committee, and all animals received humane care in accordance with guidelines established by the Canadian Council on Animal Care