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041 CAPSAICIN-SENSITIVE SENSORY NEURONS REGULATE HYPERDYNAMIC CIRCULATION IN PORTAL-HYPERTENSIVE RATS VIA C-FOS H Liu1, N Schuelert2, JJ McDougall2, SS Lee1 BACKGROUND & AIMS: Hyperdynamic circulation in portal-hypertensive rats is dependent on central neural c-fos gene expression, but how the portal-hypertensive signal activates c-fos gene expression remains obscure. In general, afferent nerves transfer signals from the periphery to the brain. The present study is to elucidate the afferent pathway from mensentery to central nerve system.
1Liver Unit, GI Group; 2Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary, Alberta
METHODS: Cervical vagus nerves were surgically isolated through a neck incision, the isolated segments were wrapped with capsaicin-soaked cotton swabs for 30 min, Portal vein stenosis (PVS) was performed 3 weeks later after the capsaicin treatment. To confirm the efficacy of vagal ablation, neural tracer horseradish peroxidase conjugated to cholera toxin (CT-HRP) was injected in the subdiaphragmatic esophagus and HRP activity was measured in nucleus tractus solitarius (NTS) 3 days later. Fos, the protein product of the c-fos gene, was detected by immunohistochemistry in central cardiovascular-regulatory nuclei. Cardiac output (CO) and mean arterial pressure (MAP) were recorded. To record the afferrent nerve activity, the vagus nerve was isolated by a middle neck incision and cut as rostrally as possible and the myelin sheath was removed. Fine neurofilaments were dissected from the nerve using fine watchmaker forceps. Nerve fibres were then placed over a platinum electrode to permit extracellular recording. For statistical analysis spikes (nerve activity) per minute were recorded and counted before and after portal vein occlusion.
RESULTS: In capsaicin-treated rats, no HRP activity was detected in the NTS after CT-HRP injection. Capsaicin treated rats subjected to PVS, Fos expression was significantly decreased in both NTS and paraventricular nucleus (PVN) nuclei compared with PVS only. Portal vein hypertension can activate vagal nerve activity. Concomitant with these neural changes, the hyperdynamic circulation was significantly decreased in capsaicin treated portal-hypertensive rats. Capsaicin induced no neural or hemodynamic changes in sham-operated controls.
CONCLUSIONS: The activation of central cardiovascular-regulatory nuclei, through a Fos-dependent pathway, is necessary for development of hyperdynamic circulation in portal-hypertensive rats. The signalling pathway from the portal venous bed to the CNS is via capsaicin-sensitive vagal afferent nerves.