Melatonin modulates baroreflex control via area postrema

Luciana A Campos, Jose Cipolla-Neto, Lisete C Michelini, Luciana A Campos, Jose Cipolla-Neto, Lisete C Michelini

Abstract

Pineal gland and its hormone melatonin have been implicated in modulation of cardiovascular system. We aimed at studying the effects of melatonin on baroreflex sensitivity and the role of area postrema, as a component modulator of baroreflex arch. Mean arterial pressure (MAP) and heart rate (HR) were recorded in conscious freely moving rats. Baroreceptor reflex sensitivity was assessed by determining the HR responses to ramped infusions of phenylephrine (PE) and sodium nitroprusside (SNP)-induced MAP changes. Melatonin bolus (0.11 mg/kg) immediately followed by its continuous infusion (0.43 × 10(-9) mol/L at a rate of 0.65 mL/h for 30 min) in healthy normotensive rats produced a downward shift of baroreceptor reflex control with a substantial inhibition of reflex tachycardia (-32%) and potentiation of reflex bradycardia (+20%). Ablation of area postrema (APX group) induced a sustained decrease of MAP (101 ± 3 vs. 116 ± 3 mmHg, P < 0.05 in comparison with sham rats, respectively). The melatonin-induced alterations of baroreflex function observed in the sham group were abolished in the APX group. We conclude that circulating melatonin can modulate baroreceptor reflex control of HR, thus resetting it toward lower HR values. The modulatory effects of melatonin may be mediated via melatonin receptors in the area postrema, located outside the blood-brain barrier.

Keywords: Area postrema; baroreflex; blood pressure; heart rate; melatonin.

Figures

Figure 1
Figure 1
Photomicrographs showing histological sections of an intact area postrema (A) and of area postrema electrolytically lesioned (B and C). Figure 1B and C characterize two types of lesions obtained: cell death (black cells) and their complete removal, respectively.
Figure 2
Figure 2
Avarage values of mean arterial pressure (MAP) and heart rate (HR) in sham-operated (n = 6) and area postrema-ablated group (APX, n = 6). Measurements were made during intravenous infusions of vehicle (VEH) and melatonin (MEL) in conscious rats. Significances (P < 0.05): * versus sham group, # versus VEH.
Figure 3
Figure 3
Average of logistic function curve with the relation between mean arterial pressure (MAP) and heart rate (HR) during intravenous administration of vehicle (VEH) or melatonin (MEL) in conscious sham-operated animals and area postrema (APX)-ablated group. Significances are shown in Table 1.

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