Peripheral Dopamine 2-Receptor Antagonist Reverses Hypertension in a Chronic Intermittent Hypoxia Rat Model
The sleep apnea-hypopnea syndrome (SAHS) involves periods of intermittent hypoxia, experimentally reproduced by exposing animal models to oscillatory PO<sub>2</sub> patterns. In both situations, chronic intermittent hypoxia (CIH) exposure produces carotid body (CB) hyperactivation genera...
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MDPI AG
2020-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/14/4893 |
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| author | Elena Olea Inmaculada Docio Miguel Quintero Asunción Rocher Ana Obeso Ricardo Rigual Angela Gomez-Niño |
| author_facet | Elena Olea Inmaculada Docio Miguel Quintero Asunción Rocher Ana Obeso Ricardo Rigual Angela Gomez-Niño |
| author_sort | Elena Olea |
| collection | DOAJ |
| description | The sleep apnea-hypopnea syndrome (SAHS) involves periods of intermittent hypoxia, experimentally reproduced by exposing animal models to oscillatory PO<sub>2</sub> 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. |
| first_indexed | 2024-03-10T18:32:18Z |
| format | Article |
| id | doaj.art-1ba49b5c849f4e6286fe07391cc51793 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T18:32:18Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-1ba49b5c849f4e6286fe07391cc517932023-11-20T06:28:45ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-07-012114489310.3390/ijms21144893Peripheral Dopamine 2-Receptor Antagonist Reverses Hypertension in a Chronic Intermittent Hypoxia Rat ModelElena Olea0Inmaculada Docio1Miguel Quintero2Asunción Rocher3Ana Obeso4Ricardo Rigual5Angela Gomez-Niño6Departamento de Enfermería, Universidad de Valladolid, 47005 Valladolid, SpainDepartamento de Bioquímica, Biología Molecular y Fisiología, Universidad de Valladolid, 47005 Valladolid, SpainDepartamento de Bioquímica, Biología Molecular y Fisiología, Universidad de Valladolid, 47005 Valladolid, SpainInstituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas-Universidad de Valladolid, 47005 Valladolid, SpainInstituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas-Universidad de Valladolid, 47005 Valladolid, SpainInstituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas-Universidad de Valladolid, 47005 Valladolid, SpainInstituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas-Universidad de Valladolid, 47005 Valladolid, SpainThe sleep apnea-hypopnea syndrome (SAHS) involves periods of intermittent hypoxia, experimentally reproduced by exposing animal models to oscillatory PO<sub>2</sub> 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.https://www.mdpi.com/1422-0067/21/14/4893chronic intermittent hypoxiacarotid bodyhypertensiondopaminedomperidoneperipheral dopamine antagonist |
| spellingShingle | Elena Olea Inmaculada Docio Miguel Quintero Asunción Rocher Ana Obeso Ricardo Rigual Angela Gomez-Niño Peripheral Dopamine 2-Receptor Antagonist Reverses Hypertension in a Chronic Intermittent Hypoxia Rat Model International Journal of Molecular Sciences chronic intermittent hypoxia carotid body hypertension dopamine domperidone peripheral dopamine antagonist |
| title | Peripheral Dopamine 2-Receptor Antagonist Reverses Hypertension in a Chronic Intermittent Hypoxia Rat Model |
| title_full | Peripheral Dopamine 2-Receptor Antagonist Reverses Hypertension in a Chronic Intermittent Hypoxia Rat Model |
| title_fullStr | Peripheral Dopamine 2-Receptor Antagonist Reverses Hypertension in a Chronic Intermittent Hypoxia Rat Model |
| title_full_unstemmed | Peripheral Dopamine 2-Receptor Antagonist Reverses Hypertension in a Chronic Intermittent Hypoxia Rat Model |
| title_short | Peripheral Dopamine 2-Receptor Antagonist Reverses Hypertension in a Chronic Intermittent Hypoxia Rat Model |
| title_sort | peripheral dopamine 2 receptor antagonist reverses hypertension in a chronic intermittent hypoxia rat model |
| topic | chronic intermittent hypoxia carotid body hypertension dopamine domperidone peripheral dopamine antagonist |
| url | https://www.mdpi.com/1422-0067/21/14/4893 |
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