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To support a long-lasting antihypertensive effect of transdermal clonidine (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 conscious spontaneously hypertensive rats. Plasma NE levels were significantly reduced for 24 h during transdermal application of clonidine patch at 1.5 and 4.5 mg/kg on the back of each rat. Oral clonidine at 100 microgram/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 during an 8-24 h period following transdermal clonidine at 1.5 and 4.5 mg/kg, respectively. Significant decrease in urinary NE excretion was also produced during a 4-8 h period following oral clonidine at 100 micrograms/kg. Total urinary NE excretion during a 0-24 h period was dose-dependently reduced following transdermal clonidine, but was not altered following oral dosing. These findings suggest that the sympathoinhibitory effect of transdermal clonidine is more persistent than that of oral clonidine. Therefore, long-lasting antihypertensive effect of transdermal clonidine is closely associated with the sustained suppression of the sympathetic nervous activity.
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