Midcervical vagotomy precludes respiratory response to novel anti-inflammatory and anti-tumour drug arvanil in rats.

Arvanil is a metabolically stable hybrid between anandamide and capsaicin. The present study was designed to test the role of the vagal pathway in post-arvanil respiratory and blood pressure responses. Respiratory and pressure changes evoked by an intravenous injection of arvanil were investigated in 21 urethane-chloralose anaesthetised and spontaneously breathing rats. In control neurally intact rats the effects of arvanil were checked to establish the appropriate dose of the drug. In the experimental group rats were challenged with arvanil while intact, following bilateral midcervical vagotomy and after subsequent supranodose vagotomy. In all neurally intact animals bolus injection of 0.8 mg/kg of arvanil into the right femoral vein induced a significant increase of tidal volume (+1+/-0.11 ml; P<0.01) and diaphragm activity (+1.72+/-0.1 arbitrary units; P<0.01) as well as hypertension (+31.9+/-2.9 mm Hg; P<0.001) and a fall in respiratory rate (-24.7+/-0.4 breath/min; P<0.001). Bilateral midcervical vagotomy precluded the alteration of respiratory parameters but did not eliminate blood pressure response. Arvanil-induced increase in mean arterial blood pressure still persisted after supranodose vagotomy. Results indicated that the respiratory effects evoked by arvanil administered via the peripheral circulation require intact midcervical vagi. Supranodose vagotomy failed to eliminate the hypertension evoked by arvanil.