Rilmenidine (S 3341) and the sympathoadrenal system: adrenoreceptors, plasma and adrenal catecholamines in dogs.
1. The effects of rilmenidine, a new alpha 2-adrenoreceptor agonist with antihypertensive properties, were investigated on plasma catecholamines, blood cell adrenoreceptors and adrenal medullary function. 2. In conscious sino-aortic denervated (SAD) dogs, rilmenidine (1 mg kg-1 orally for 2 weeks) significantly reduced both blood pressure and heart rate when compared with placebo treatment. The drug decreased plasma noradrenaline and adrenaline levels and corrected the decrease in leucocyte beta-adrenoreceptors observed in placebo-treated SAD dogs. There was no change in platelet alpha 2-adrenoreceptors. 3. In anaesthetized normotensive dogs, rilmenidine (0.1 and 0.3 mg kg-1 i.v.) induced a dose-dependent decrease in both cardiovascular parameters (blood pressure and heart rate) and catecholamine release from the adrenal medulla. 4. The present study shows that rilmenidine decreases sympathetic tone mainly by an action on the adrenal medulla. In addition, its ability to lower blood pressure in SAD dogs, i.e. a model of hypertension in which high sympathetic tone is present, indicates that rilmenidine may also depress other parts of the sympathetic nervous system.
Valet
P
P
Laboratoire de Pharmacologie Médicale et Clinique, INSERM U 317, Faculté de Médecine, Toulouse, France.
Tran
M A
MA
Damase-Michel
C
C
de Saint-Blanquat
G
G
Dang Tran
L
L
Anglade
F
F
Koenig-Berard
E
E
Montastruc
J L
JL
D000313:Adrenal Medulla / Q000187:drug effects* / Q000378:metabolism; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001792:Blood Platelets / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000378:metabolism*; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects; D007962:Leukocytes / Q000378:metabolism; D010080:Oxazoles / Q000494:pharmacology*; D000077769:Rilmenidine; D013564:Sympathetic Nervous System / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D002395:Catecholamines; D010080:Oxazoles; D000077769:Rilmenidine