Effects of long-term pretreatment with isoproterenol on bromocriptine-induced tachycardia in conscious rats

It has been shown that bromocriptine-induced tachycardia, which persisted a fter adrenalectomy, is (i) mediated by central dopamine D-2 receptor activa tion and (ii) reduced by 5-day isoproterenol pretreatment, supporting there fore the hypothesis that this effect is dependent on sympathetic outflow to the heart. This study was conducted to examine whether prolonged pretreatm ent with isoproterenol could abolish bromocriptine-induced tachycardia in c onscious rats. Isoproterenol pretreatment for 15 days caused cardiac hypert rophy without affecting baseline blood pressure and heart rate. In control rats, intravenous bromocriptine (150 mu g/kg) induced significant hypotensi on and tachycardia. Bromocriptine-induced hypotension was unaffected by iso proterenol pretreatment, while tachycardia was reversed to significant brad ycardia, an effect that was partly reduced by i.v. domperidone (0.5 mg/kg). Neither cardiac vagal nor sympathetic tone was altered by isoproterenol pr etreatment. In isolated perfused heart preparations from isoproterenol-pret reated rats, the isoproterenol-induced maximal increase in left ventricular systolic pressure was significantly reduced, compared with saline-pretreat ed rats (the EC50 of the isoproterenol-induced increase in left ventricular systolic pressure was enhanced similar to 22-fold). These results show tha t 15-day isoproterenol pretreatment not only abolished but reversed bromocr iptine-induced tachycardia to bradycardia, an effect that is mainly related to further cardiac beta-adrenoceptor desensitization rather than to impair ment of autonomic regulation of the heart. They suggest that, in normal con scious rats, the central tachycardia of bromocriptine appears to predominat e and to mask the bradycardia of this agonist at peripheral dopamine D-2 re ceptors.