Studies on the centrally mediated hypotensive activity of guanabenz.

Prior studies demonstrated that guanabenz reduces systemic blood pressure by inhibiting central sympathetic outflow as well as by adrenergic neuron blockade. Potential mechanisms responsible for the reduction of efferent sympathetic activity were examined in the present series. Guanabenz failed to modify carotid sinus nerve activity in a perfused sinus preparation. It reduced sympathetic outflow, heart rate and blood pressure in debuffered cats indicating that its actions are not mediated primarily by baroreceptor mechanisms. alpha-Adrenergic blockade greatly attenuated the response suggesting that the central sympathoinhibitory effect of guanabenz results from alpha-adrenergic receptor activation. Only a high dose of the compound attenuated the increase in sympathetic nerve activity produced by stimulation of the posterior hypothalamus. These experiments lead to the overall conclusion that guanabenz acts primarily at sites which regulate the basal level of sympathetic outflow.