In Vivo Evidence That Endogenous Dopamine Modulates Sympathetic Activity in Man

Mannelli, Massimo; Ianni, Lucia; Lazzeri, Chiara; Castellani, Walter; Pupilli, Cinzia; Villa, Giorgio La; Barletta, Giuseppe; Serio, Mario; Franchi, F

doi:10.1161/01.hyp.34.3.398

Cited by 43 publications

(32 citation statements)

References 21 publications

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“…In previous studies, 26,27 we have demonstrated that D 2 -like receptors are present on human chromaffin cells and that they An example of power spectra at baseline (top), after bromocriptine administration (middle), and after DMϩbromocriptine treatment (bottom), with subjects in the supine position (left) and the sitting position (right). PSD indicates power spectrum density.…”

Section: Discussionmentioning

confidence: 99%

Centrally Mediated Effects of Bromocriptine on Cardiac Sympathovagal Balance

et al. 2001

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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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Section: Discussionmentioning

confidence: 99%

Centrally Mediated Effects of Bromocriptine on Cardiac Sympathovagal Balance

et al. 2001

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“…22 As leptin-binding sites have been found in regions of the brain that are important in cardiovascular control, 23 and chronic leptin infusion exerts longterm effects on cardiovascular and renal function, 12,24 it seems conceivable that leptin could modify cardiovascular function through central nervous system effects. Evidence suggests that endogenous DA modulates NE synthesis and secretion in the noradrenergic neurons 25 and -at least in part -leptin release and OB gene expression in adipose tissue. As DAergic activity is reduced in subjects with hypertension and obesity, 3 this could explain in part that obesity, 26 sympathetic hyperactivity, 27 and hyperleptinemia 28 are associated with hypertension.…”

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confidence: 99%

Effects of dopamine on leptin release and leptin gene (OB) expression in adipocytes from obese and hypertensive patients

Álvarez-Aguilar¹,

Alvarez-Paredes²,

Lindholm³

et al. 2013

IJNRD

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Background A reduction of dopaminergic (DAergic) activity with increased prolactin levels has been found in obese and hypertensive patients, suggesting its involvement as a pathophysiological mechanism promoting hypertension. Similarly, leptin action increasing sympathetic activity has been proposed to be involved in mechanisms of hypertension. The aim of this study was to analyze the effects of DA, norepinephrine (NE), and prolactin on leptin release and leptin gene ( OB ) expression in adipocytes from obese and hypertensive patients. Methods Leptin release and OB gene expression were analyzed in cultured adipocytes from 16 obese and hypertensive patients treated with DA (0.001, 0.01, 0.1, and 1.0 μmol/L), NE (1.0 μmol/L), insulin (0.1 μmol/L), and prolactin (1.0 μmol/L), and from five nonobese and normotensive controls treated with DA (1 μmol/L), NE (1 μmol/L), insulin (0.1 μmol/L), and prolactin (1.0 μmol/L). Results A dose-related reduction of leptin release and OB gene messenger ribonucleic acid expression under different doses of DA was observed in adipocytes from obese hypertensive patients. Whereas prolactin treatment elicited a significant increase of both leptin release and OB gene expression, NE reduced these parameters. Although similar effects of DA and NE were observed in adipocytes from controls, baseline values in controls were reduced to 20% of the value in adipocytes from obese hypertensive patients. Conclusion These results suggest that DAergic deficiency contributes to metabolic disorders linked to hyperleptinemia in obese and hypertensive patients.

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“…During intense sympathetic activation, as induced by physical exercise, D 2 -like antagonists cause a larger increase in plasma norepinephrine than placebo (31). These data suggest that during a high degree of sympathetic stimulation, endogenous dopamine, which is co-released with norepinephrine by nerve endings, is sufficiently increased in the synaptic cleft to modulate and inhibit norepinephrine release (29).…”

Section: Possible Mechanisms In the Inhibition To Dopamine And Quinpimentioning

confidence: 88%

“…This could explain the bradycardia induced by the highest doses of dopamine and quinpirole (see Table 2). The source of endogenous dopamine acting on the presynaptic D 2 -receptors is still unknown (29). Other studies on heart rate have shown that D 2 -like antagonists did not modify plasma norepinephrine in humans when administered in conditions of rest or mild sympathetic stimulation, which is achieved by standing, a cold pressor test, or hand-grip (30).…”

Section: Possible Mechanisms In the Inhibition To Dopamine And Quinpimentioning

confidence: 99%

Pharmacological Evidence That Dopamine Inhibits the Cardioaccelerator Sympathetic Outflow via D2-Like Receptors in Pithed Rats

et al. 2013

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Abstract. It has been suggested that N,N-di-n-propyl-dopamine (dopamine analogue) decreased heart rate in rats through stimulation of dopamine receptors. Nevertheless, the role of prejunctional dopamine D 1/2 -like receptors or even a 2 -adrenoceptors to mediate cardiac sympatho-inhibition induced by dopamine remains unclear. Hence, this study identified the pharmacological profile of the cardiac sympatho-inhibition to dopamine in pithed rats. Male Wistar rats were pithed and prepared to stimulate the cardiac sympathetic outflow or to receive i.v. bolus of exogenous noradrenaline. I.v. continuous infusions of dopamine (endogenous ligand) or quinpirole (D 2 -like agonist) dose-dependently inhibited the tachycardic responses to sympathetic stimulation, but not those to exogenous noradrenaline. In contrast, SKF-38393 (100 mg/kg•min, D 1 -like agonist) failed to modify both of these responses. The sympatho-inhibition to dopamine (1.8 mg/kg•min) or quinpirole (100 mg/kg•min): i) remained unaltered after saline or the antagonists SCH-23390 (D 1 -like, 300 mg/kg) and rauwolscine (a 2 -adrenoceptors, 300 mg/kg); and ii) was significantly antagonized by raclopride (D 2 -like, 300 mg/kg). These antagonists, at the above doses, failed to modify the sympatheticallyinduced tachycardic responses. The above results suggest that the inhibition of the cardiac sympathetic outflow to dopamine and quinpirole is primarily mediated by prejunctional D 2 -like receptors but not D 1 -like receptors or a 2 -adrenoceptors.

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In Vivo Evidence That Endogenous Dopamine Modulates Sympathetic Activity in Man

Cited by 43 publications

References 21 publications

Centrally Mediated Effects of Bromocriptine on Cardiac Sympathovagal Balance

Centrally Mediated Effects of Bromocriptine on Cardiac Sympathovagal Balance

Effects of dopamine on leptin release and leptin gene (OB) expression in adipocytes from obese and hypertensive patients

Pharmacological Evidence That Dopamine Inhibits the Cardioaccelerator Sympathetic Outflow via D2-Like Receptors in Pithed Rats

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