Abstract
The sleep apnea-hypopnea syndrome (SAHS) involves periods of intermittent hypoxia, experimentally reproduced by exposing animal models to oscillatory PO2 patterns. In both situations, chronic intermittent hypoxia (CIH) exposure produces carotid body (CB) hyperactivation generating an increased input to the brainstem which originates sympathetic hyperactivity, followed by hypertension that is abolished by CB denervation. CB has dopamine (DA) receptors in chemoreceptor cells acting as DA-2 autoreceptors. The aim was to check if blocking DA-2 receptors could decrease the CB hypersensitivity produced by CIH, minimizing CIH-related effects. Domperidone (DOM), a selective peripheral DA-2 receptor antagonist that does not cross the blood-brain barrier, was used to examine its effect on CIH (30 days) exposed rats. Arterial pressure, CB secretory activity and whole-body plethysmography were measured. DOM, acute or chronically administered during the last 15 days of CIH, reversed the hypertension produced by CIH, an analogous effect to that obtained with CB denervation. DOM marginally decreased blood pressure in control animals and did not affect hypoxic ventilatory response in control or CIH animals. No adverse effects were observed. DOM, used as gastrokinetic and antiemetic drug, could be a therapeutic opportunity for hypertension in SAHS patients’ resistant to standard treatments.
Highlights
The sleep apnea-hypopnea syndrome (SAHS) involves episodes of total or partial closure of the upper airway during sleep giving rise to periods of intermittent hypoxia, sleep fragmentation and inspiratory efforts
It is known that the carotid body (CB) expresses high levels of dopamine D2 receptors (D2R) located in the carotid sinus nerve and in chemoreceptor cells [13,14] which are negatively coupled to adenyl cyclase and calcium channels, and activate inhibitory G-protein-activated inwardly rectifying potassium channels [15]
The study was designed to test the hypothesis that blocking D2R on peripheral chemoreceptors could modify the CB hypersensitivity produced by chronic exposure to intermittent hypoxia and to minimize chronic intermittent hypoxia (CIH) related effects
Summary
The sleep apnea-hypopnea syndrome (SAHS) involves episodes of total or partial closure of the upper airway during sleep giving rise to periods of intermittent hypoxia, sleep fragmentation and inspiratory efforts. The CB is a dopaminergic organ in most species [12] but the functional meaning of dopamine (DA) is controversial, mainly due to the presence of DA receptors in the carotid sinus nerve endings, the efferent sensory nerve innervating the CB, and in the chemoreceptor cells. The study was designed to test the hypothesis that blocking D2R on peripheral chemoreceptors could modify the CB hypersensitivity produced by chronic exposure to intermittent hypoxia and to minimize CIH related effects. We administered acute or chronic DOM to rats exposed to CIH and we found that DOM reversed the hypertension induced by CIH exposure This observation could be due to a CIH CB desensitization, producing a similar effect to that obtained with CB denervation. DOM is used as a gastro-esophageal motility regulator and antiemetic drug with no major side effects [21]
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