Location of the mechanism of the clonidine withdrawal tachycardia in rats

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Abstract
Withdrawal of chronic infusion of clonidine elicits severe tachycardia and short-lasting blood pressure elevations (upswings). Withdrawal of clonidine in low dosage (30 μg kg−1 day−1 i.c.v., 7 days) elicited a maximum of 10.9 ± 0.5 upswings h−1. Cessation of s.c. infusion of clonidine (30 μg kg−1 day−1 7 days) evoked a maximum of 1.9 ± 0.5 upswings h−1. After cessation of the two clonidine infusions no overshoot of heart rate occurred. Withdrawal of a higher dose of clonidine (300 μg kg−1 day−1 s.c., 7 days), however, induced tachycardia (from 302 ± 8 to 433 ± 8 beats min−1) and 7.6 ± 1.4 upswings h−1. The administration of the α2-adrenoceptor antagonist yohimbine precipitated withdrawal tachycardia in animals treated with oxymetazoline, a hydrophilic α-adrenoceptor agonist. Yohimbine (3 mg kg−1 i.p.) precipitated a severe rise in heart rate from 285 ± 14 to 520 ± 5 beats min−1 in oxymetazoline (300 μg kg−1 day−1s.c., 7 days) treated rats and from 320 ± 13 to 420 ± 11 beats min−1 in saline-treated animals. Upswings were not induced by yohimbine treatment. It is concluded, that the blood pressure upswings after clonidine withdrawal are due to a central mechanism, whereas the mechanism of the overshoot of heart rate is located peripherally, probably at the cardiac presynaptic level.