CHANGES IN PLASMA AND URINARY NOREPINEPHRINE FOLLOWING TRANSDERMAL CLONIDINE IN SPONTANEOUSLY HYPERTENSIVE RATS

To support a long-lasting antihypertensive effect of transdermal cloni dine (CAS 4205-90-7), changes in plasma norepinephrine (NE) levels and urinary NE excretion as indices of the sympathetic nervous activities were investigated following transdermal and oral clonidine in conscio us spontaneously hypertensive rats. Plasma NE levels were significantl y reduced for 24 h during transdermal application of clonidine patch a t 1.5 and 4.5 mg/kg on the back of each rat. Oral clonidine at 100 mu g/kg also lowered plasma NE levels. However, significant falls in the levels lasted only for 4 h after oral dosing. Urinary NE excretion was significantly decreased during both 4-8 and 8-24 h periods, and durin g an 8-24 h period following transdermal clonidine at 1.5 and 4.5 mg/k g, respectively. Significant decrease in urinary NE excretion was also produced during a 4-8 h period following oral clonidine at 100 mu g/k g. Total urinary NE excretion during a 0-24 h period was dose-dependen tly reduced following transdermal clonidine, but was not altered follo wing oral dosing. These findings suggest that the sympathoinhibitory e ffect of transdermal clonidine is more persistent than that of oral cl onidine. Therefore, long-lasting antihypertensive effect of transderma l clonidine is closely associated with the sustained suppression of th e sympathetic nervous activity.