Preventive effect of rilmenidine on the occurrence of neurogenic ventricular arrhythmias in rabbits.
BACKGROUND
Centrally acting antihypertensive drugs bearing an imidazoline or a related chemical structure inhibit sympathetic nervous output to the heart and vascular beds, and enhance parasympathetic tone. Cardiac ischaemia and ventricular arrhythmias that can result from hypertension are likely to benefit from such effects.


OBJECTIVE
To investigate the effects of rilmenidine, an oxazoline with antihypertensive properties, in a model of neurogenically induced ischaemic ventricular arrhythmias.


RESULTS
Bicuculline, a alpha-aminobutyric acid (GABA(A)) receptor antagonist, was administered intracisternally in pentobarbitone anaesthetized rabbits; 10 microg/kg intracisternal bicuculline induced polymorphic ventricular ectopic beats and ventricular tachycardia, while blood pressure increased by about 50-60% and heart rate in sinus rhythm decreased by about 20%. Rilmenidine pretreatment (10 min), either administered intravenously (0.01, 0.1, 1 mg/kg) or intracisternally (3, 10, 30 microg/kg), dose-dependently prevented the occurrence of bicuculline-induced arrhythmias and, because of a lower baseline, the blood pressure values reached were less when compared with controls. Intracisternal idazoxan (15 microg/kg) had no significant antiarrhythmic effect but antagonized, in part, the haemodynamic and antiarrhythmic effects of rilmenidine (1 mg/kg intravenously; 30 microg/kg intracisternally).


CONCLUSIONS
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 from action on the central as well as on the peripheral nervous systems. Direct coronary or cardiac effects might also play a role, in particular at low non-hypotensive intravenous doses.
Roegel
J C
JC
Laboratoire de Pharmacologie Cardiovasculaire et Rénale, CNRS ERS 109, Faculté de Médecine, Strasbourg, France.
Yannoulis
N
N
De Jong
W
W
Feldman
J
J
Bousquet
P
P
D000818:Animals; D000959:Antihypertensive Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001640:Bicuculline; D005117:Cardiac Complexes, Premature / Q000139:chemically induced / Q000209:etiology / Q000517:prevention & control*; D018756:GABA Antagonists; D006439:Hemodynamics / Q000187:drug effects; D019329:Idazoxan / Q000494:pharmacology; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D010080:Oxazoles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011817:Rabbits; D000077769:Rilmenidine; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology; D017180:Tachycardia, Ventricular / Q000139:chemically induced / Q000517:prevention & control*
D000959:Antihypertensive Agents; D018756:GABA Antagonists; D010080:Oxazoles; D000077769:Rilmenidine; D019329:Idazoxan; D001640:Bicuculline