Central dopaminergic origin of bromocriptine induced tachycardia in normotensive rats.
OBJECTIVE
This study was undertaken to investigate the mechanism of the tachycardic effect of bromocriptine, a specific dopamine D-2 receptor agonist, which is not abolished, as previously reported, by intravenous domperidone, a selective dopamine D-2 antagonist unable to cross the blood brain barrier. Two hypotheses were tested: (1) that the increase in heart rate after intravenous treatment with bromocriptine could be related to central dopamine receptor stimulation and (2) that it could be induced by a release of adrenaline from the adrenal medulla.


METHODS
Changes in mean aortic pressure and heart rate, induced by treatment with 150 micrograms.kg-1 bromocriptine intravenously, were measured in conscious or anaesthetised normal or adrenalectomised rats submitted to various pretreatments.


RESULTS
In conscious intact rats, intravenous bromocriptine decreased mean aortic pressure (-11 (SEM1) mm Hg) and increased heart rate (62(12)) beats.min-1). Both effects were prevented by intravenous pretreatment (0.3 mg.kg-1) with dopamine D-2 receptor antagonists able to cross the blood brain barrier, such as haloperidol, sulpiride, and metoclopramide. In anaesthetised rats, domperidone (50 and 20 micrograms.kg-1) given via a lateral cerebral ventricle abolished the bromocriptine induced tachycardia without affecting the hypotensive response. Both effects were unchanged after bilateral adrenalectomy but were completely abolished by intravenous haloperidol pretreatment (0.3 mg.kg-1) in conscious adrenalectomised rats.


CONCLUSIONS
These results suggest that in anaesthetised and conscious normotensive rats, the bromocriptine induced tachycardia is not related to a release of adrenaline from the adrenal medulla but could be elicited by central dopamine D-2 receptor stimulation through a possible increase in cardiac sympathetic tone.
Lahlou
S
S
Laboratoire de Physiologie et Pharmacologie, URA CNRS 1287, Faculté de Pharmacie, La Tronche, France.
Duarte
G P
GP
Demenge
P
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D000315:Adrenalectomy; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001971:Bromocriptine / Q000494:pharmacology*; D004294:Domperidone / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D006220:Haloperidol / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013469:Sulpiride / Q000494:pharmacology; D013610:Tachycardia / Q000139:chemically induced*
D065127:Dopamine D2 Receptor Antagonists; D001971:Bromocriptine; D004294:Domperidone; D013469:Sulpiride; D006220:Haloperidol; D008787:Metoclopramide