Synthetic capsaicin reversibly impairs vasopressin-mediated blood pressure recovery.

The vasopressin-mediated recovery of arterial pressure observed in adult rats following pharmacological blockade of the sympathetic nervous and renin-angiotensin systems is reduced by neonatal capsaicin treatment. We now demonstrate a similar but reversible effect following treatment of adult Wistar or Sprague-Dawley rats with N-vanillylnonanamide (50 mg/kg sc). One day after treatment, Wistar, but typically not Sprague-Dawley, rats had lost weight and exhibited increased sensitivity to the anesthetic effects of methohexital sodium. In both strains, captopril treatment caused hypotension. After captopril and ganglionic blockade, vasopressin-mediated recovery of arterial pressure was significantly inhibited. Furthermore, treated Wistar rats had reduced sensitivity to the ocular irritancy of N-vanillylnonanamide when examined 2 days postdose. All deficits reversed within 2 wk of dosing. These data suggest that capsaicin-sensitive systems participate in homeostatic mechanisms engaged during acute hypotension. Because the dose of N-vanillylnonanamide employed in the present study has previously been shown to destroy unmyelinated afferent fibers when administered to adult rats, recovery of the functional deficits may reflect regeneration of damaged processes or assumption of their function by undamaged neurons innervating adjacent sites. By extrapolation from other studies of capsaicin, damage to some central neurons may also be involved.