Peripheral Dopamine 2-Receptor Antagonist Reverses Hypertension in a Chronic Intermittent Hypoxia Rat Model

• Main Authors: Elena Olea, Inmaculada Docio, Miguel Quintero, Asunción Rocher, Ana Obeso, Ricardo Rigual, Angela Gomez-Niño
• Format: Article
• Language: English
• Published: MDPI AG 2020-07-01
• Series: International Journal of Molecular Sciences
• Subjects: chronic intermittent hypoxia; carotid body; hypertension; dopamine; domperidone; peripheral dopamine antagonist
• Online Access: https://www.mdpi.com/1422-0067/21/14/4893

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.