Centrally Mediated Effects of Bromocriptine on Cardiac Sympathovagal Balance

Abstract

Abstract-Bromocriptine, a dopamine agonist, is known to lower cardiovascular mortality in L-dopa-treated patients withParkinson's disease, probably by reducing the cardiac sympathetic activity. We aimed at unmasking the central effects of bromocriptine on the heart by power spectrum analysis. Ten healthy subjects (aged 31Ϯ2 years) in supine and sitting positions were evaluated after the administration of bromocriptine (2.5 mg) alone and after pharmacological peripheral D 2 -like blockade by domperidone (20 mg). We calculated (autoregressive method) the following: the low-frequency (LF) component (an index of cardiac sympathetic tone), the high-frequency (HF) component (an index of cardiac vagal tone), and the LF/HF ratio (an index of cardiac sympathovagal balance). With subjects in the supine position, bromocriptine alone induced a significant increase in the LF component and the LF/HF ratio, together with a reduction in norepinephrine plasma levels and blood pressure values. These conflicting effects can be explained as the combined result of direct and indirect (reflex-mediated) actions of bromocriptine in vivo. No changes in cardiac autonomic drive were observed with subjects in the sitting position. After domperidone pretreatment, bromocriptine induced a reduction in the LF component and in the LF/HF ratio. The sitting position caused an increase in heart rate and in the LF/HF ratio. We demonstrated both peripheral and central effects of bromocriptine. In particular, pretreatment with a peripheral antagonist (domperidone) allowed us to unmask the central effect of bromocriptine on cardiac sympathetic drive. Key Words: autonomic nervous system Ⅲ sympathetic nervous system Ⅲ dopamine Ⅲ heart rate B romocriptine is a D 2 -like receptor agonist that is known to inhibit sympathetic output and to lower the cardiovascular mortality in L-dopa-treated patients with Parkinson's disease. 1 The cardioprotective effect of bromocriptine can be related to a withdrawal of the cardiac sympathetic activity, which could diminish the risk of potentially lifethreatening ventricular arrhythmias. As a matter of fact, it has been shown in experimental animals that bromocriptine increases the ventricular fibrillation threshold by 50% 2 and decreases plasma levels of catecholamines. 3 Whereas peripheral actions of bromocriptine have been well elucidated not only under resting conditions 4 but also in response to hemodynamic maneuvers, 5-7 a centrally mediated reduction in sympathetic outflow has not been demonstrated so far.With this in mind, the design of the present study was aimed at evaluating the effects of acute bromocriptine administration on cardiac sympathovagal balance by means of power spectral analysis. Taking into account that domperidone (DM) is a peripheral D 2 -like receptor antagonist that is able to counteract the peripheral effects of bromocriptine, 8,9 we analyzed the influence of preadministration of DM on the sympathovagal balance with subjects in supine and sitting positions to unmask the central activity of br...

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