Central Bromocriptine‐Induced Tachycardia is Reversed to Bradycardia in Conscious, Deoxycorticosterone Acetate‐Salt Hypertensive Rats

Abstract

A central dopaminergic origin has been demonstrated for the bromocriptine-induced tachycardia in conscious, normotensive rats. The present study investigated the effect of bromocriptine on heart rate and the principal site of action of this agonist in conscious, deoxycorticosterone acetate-salt hypertensive rats, in which altered central dopaminergic activity has been previously reported. Intravenous administration of bromocriptine (150 mg/kg) increased heart rate (49∫5 beats/min.) in uninephrectomized control rats, while it induced a significant bradycardia (50∫6 beats/min.) in deoxycorticosterone acetate-salt hypertensive rats. In the latter animals, intravenous (500 mg/kg) or intrathecal (40 mg/rat at T 9 -T 10 ) pretreatment with domperidone, a selective dopamine D 2 receptor antagonist that does not cross the blood-brain barrier, reduced partially, but significantly, the bradycardiac responses to bromocriptine (reduction of about 44% and 48% of the maximal effect, respectively). In contrast, the bromocriptine-induced bradycardia was fully abolished by intravenous pretreatment with metoclopramide (300 mg/kg), a dopamine D 2 receptor antagonist that crosses the blood-brain barrier, or by combined pretreatment with intravenous and intrathecal domperidone. These results indicate that, in deoxycorticosterone acetate-salt hypertensive rats, bromocriptine decreases rather than increases heart rate, an effect that is mediated partly through a peripheral D 2 dopaminergic mechanism and partly through stimulation of spinal dopamine D 2 receptors. They further support the concept that, in normotensive, conscious rats, the central tachycardia of bromocriptine appears to predominate and to mask the bradycardia of this agonist at both peripheral and spinal dopamine D 2 receptors.