Bromocriptine-induced tachycardia in conscious rats: blunted response following isoproterenol pretreatment for 5 days.
Previous studies have shown that tachycardia induced by intravenous injection of bromocriptine, which persisted after adrenalectomy, was mediated by central dopamine D2 receptor stimulation. Such stimulation could activate central sympathetic outflow to the heart. To test this hypothesis, we investigated whether pretreatment with isoproterenol, known to induce cardiac beta-adrenoceptor desensitization, could reduce bromocriptine-induced tachycardia. A 5 day pretreatment with isoproterenol (5 mg/kg/day) induced a 21% increase in the ratio of ventricular dry weight to body weight, compared with saline-pretreated rats. In isolated perfused heart preparations from isoproterenol-pretreated rats, the isoproterenol-induced increase in left ventricular systolic pressure and heart rate was significantly reduced, compared with saline-pretreated rats (the isoproterenol concentration producing 50% of the maximal positive inotropic and chronotropic responses was increased approximately 5- and 4-fold, respectively). In conscious control rats, intravenous injection of bromocriptine (50, 150 and 250 micrograms/kg) decreased mean aortic pressure and increased heart rate in a dose-related manner. Pretreatment with isoproterenol for 5 days reduced bromocriptine-induced tachycardia without affecting hypotension. Cardiac autonomic tone remained of the same order of magnitude irrespective of whether the animal was pretreated with isoproterenol. These results indicate that isoproterenol pretreatment reduces bromocriptine-induced tachycardia mainly through desensitization of cardiac beta-adrenoceptors rather than via an impairment of autonomic regulation of the heart. This supports the hypothesis that bromocriptine-induced activation of central dopamine D2 receptors increases heart rate via activation of central sympathetic outflow to the heart.
Departamento de Fisiologia e Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Pernambuco, Recife-PE, Brasil.
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Lahlou
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Duarte
D000318:Adrenergic beta-Agonists / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001971:Bromocriptine / Q000494:pharmacology*; D003243:Consciousness; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol / Q000627:therapeutic use*; D008297:Male; D009929:Organ Size; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D012965:Sodium Chloride / Q000627:therapeutic use*; D013610:Tachycardia / Q000139:chemically induced*; D013997:Time Factors
D000318:Adrenergic beta-Agonists; D017448:Receptors, Dopamine D2; D001971:Bromocriptine; D012965:Sodium Chloride; D007545:Isoproterenol