Guanfacine and clonidine: the effects on adrenal medullary function in spontaneously hypertensive rats

The effect of guanfacine on adrenal medullary function was investigated in anesthetized spontaneously hypertensive rats (SHR). This effect was compared with the clonidine-induced adrenal suppressant action. Sympathetic adrenal nerve activity and adrenal catecholamine secretion rate were determined and used for the analysis of adrenal medullary function. Intravenous administration of guanfacine (30-100 micrograms/kg) produced a decrease in both adrenal nerve activity and adrenal catecholamine secretion rate that paralleled a decrease in arterial blood pressure and heart rate. The ED50 of the guanfacine-induced decrease in adrenal nerve activity was 300 micrograms/kg, and the ED50 of clonidine was 30 micrograms/kg. This guanfacine dose produced decreases up to about 20% of the pretreatment values in both epinephrine and norepinephrine secretion rates from the adrenal medulla. Moreover, guanfacine produced a significant decrease of adrenal plasma flow rate. The adrenal plasma flow rate did not change significantly after clonidine administration. These findings suggest that the adrenal suppressant effect induced by guanfacine is predominantly due to its central action and that the vasoconstriction due to the peripheral action of guanfacine is partly related to its adrenal suppressant effect in SHR.