Location of the mechanism of the clonidine withdrawal tachycardia in rats.
Withdrawal of chronic infusion of clonidine elicits severe tachycardia and short-lasting blood pressure elevations (upswings). Withdrawal of clonidine in low dosage (30 micrograms 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 micrograms 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 micrograms 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 alpha 2-adrenoceptor antagonist yohimbine precipitated withdrawal tachycardia in animals treated with oxymetazoline, a hydrophilic alpha-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 micrograms kg-1 day-1 s.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.
Jonkman
F A
FA
Man
P W
PW
Thoolen
M J
MJ
van Zwieten
P A
PA
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000633:toxicity*; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D008297:Male; D010109:Oxymetazoline / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013375:Substance Withdrawal Syndrome / Q000209:etiology*; D013610:Tachycardia / Q000139:chemically induced*; D013997:Time Factors; D015016:Yohimbine / Q000494:pharmacology
D015016:Yohimbine; D010109:Oxymetazoline; D003000:Clonidine