Inhibition of centrally induced ventricular arrhythmias by rilmenidine and idazoxan in rabbits.
In a model of ventricular arrhythmias of central origin, we investigated the effects of rilmenidine, an oxazoline with antihypertensive properties, and idazoxan, an imidazoline that is an antagonist of the hypotensive effects of rilmenidine. Bicuculline, a GABAA receptor antagonist, was administered intracisternally (i.c.) to produce arrhythmias in pentobarbitone anaesthetised rabbits; 10 micrograms/kg bicuculline i.c. induced polymorphic ventricular ectopic beats and ventricular tachycardia while blood pressure increased by about 50-60% and sinusal heart rate decreased by about 20%. Rilmenidine, either administered intravenously (0.01, 0.1, 1 mg/kg i.v.) or i.c. (3, 10, 30 micrograms/kg) dose-dependently prevented the occurrence of bicuculline-induced arrhythmias while, because of a lower base-line, the blood pressure values reached were less as compared to controls. Idazoxan administered i.v. (3, 10 mg/kg) had a similar action. Idazoxan i.c. (15 micrograms/kg) had no significant antiarrhythmic effect but antagonized in part the haemodynamic and antiarrhythmic effects of rilmenidine (1 mg/kg i.v.; 30 micrograms/kg i.c.). It is suggested that the antiarrhythmic effects observed with rilmenidine are mainly mediated by blunting the bicuculline-induced increase in the sympathetic nervous output to the heart and the vascular beds. These effects of rilmenidine are likely to originate both from the central and peripheral nervous system. The antiarrhythmic effects of idazoxan i.v. might be related to a blocking action on alpha 2-adrenoceptors at the level of the coronary arteries and other vascular beds.
Roegel
J C
JC
Laboratoire de Pharmacologie Cardiovascular et Rénale, CNRS ERS 109, Faculté de Médecine, Strasbourg, France.
Yannoulis
N
N
De Jong
W
W
Monassier
L
L
Feldman
J
J
Bousquet
P
P
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000517:prevention & control*; D001640:Bicuculline; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018756:GABA Antagonists / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D019329:Idazoxan / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D008297:Male; D010080:Oxazoles / Q000008:administration & dosage / Q000494:pharmacology*; D011817:Rabbits; D000077769:Rilmenidine
D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D018756:GABA Antagonists; D010080:Oxazoles; D000077769:Rilmenidine; D019329:Idazoxan; D001640:Bicuculline