Chemogenetic inhibition of NTS astrocytes normalizes cardiac autonomic control and ameliorate hypertension during chronic intermittent hypoxia
Abstract Background Obstructive sleep apnea (OSA) is characterized by recurrent episodes of chronic intermittent hypoxia (CIH), which has been linked to the development of sympathoexcitation and hypertension. Furthermore, it has been shown that CIH induced inflammation and neuronal hyperactivation i...
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| Format: | Article |
| Language: | English |
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BMC
2023-11-01
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| Series: | Biological Research |
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| Online Access: | https://doi.org/10.1186/s40659-023-00463-0 |
| _version_ | 1827764660715126784 |
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| author | Katherin Pereyra Alexandra Las Heras Camilo Toledo Esteban Díaz-Jara Rodrigo Iturriaga Rodrigo Del Rio |
| author_facet | Katherin Pereyra Alexandra Las Heras Camilo Toledo Esteban Díaz-Jara Rodrigo Iturriaga Rodrigo Del Rio |
| author_sort | Katherin Pereyra |
| collection | DOAJ |
| description | Abstract Background Obstructive sleep apnea (OSA) is characterized by recurrent episodes of chronic intermittent hypoxia (CIH), which has been linked to the development of sympathoexcitation and hypertension. Furthermore, it has been shown that CIH induced inflammation and neuronal hyperactivation in the nucleus of the solitary tract (NTS), a key brainstem region involved in sympathetic and cardiovascular regulation. Since several studies have proposed that NTS astrocytes may mediate neuroinflammation, we aimed to determine the potential contribution of NTS-astrocytes on the pathogenesis of CIH-induced hypertension. Results Twenty-one days of CIH induced autonomic imbalance and hypertension in rats. Notably, acute chemogenetic inhibition (CNO) of medullary NTS astrocytes using Designer Receptors Exclusively Activated by Designers Drugs (DREADD) restored normal cardiac variability (LF/HF: 1.1 ± 0.2 vs. 2.4 ± 0.2 vs. 1.4 ± 0.3, Sham vs. CIH vs. CIH + CNO, respectively) and markedly reduced arterial blood pressure in rats exposed to CIH (MABP: 82.7 ± 1.2 vs. 104.8 ± 4.4 vs. 89.6 ± 0.9 mmHg, Sham vs. CIH vs. CIH + CNO, respectively). In addition, the potentiated sympathoexcitation elicit by acute hypoxic chemoreflex activation in rats exposed to CIH was also completely abolished by chemogenetic inhibition of NTS astrocytes using DREADDs. Conclusion Our results support a role for NTS astrocytes in the maintenance of heightened sympathetic drive and hypertension during chronic exposure to intermittent hypoxia mimicking OSA. |
| first_indexed | 2024-03-11T11:07:37Z |
| format | Article |
| id | doaj.art-8c7e3e02152c4b96b7c9a4f099208539 |
| institution | Directory Open Access Journal |
| issn | 0717-6287 |
| language | English |
| last_indexed | 2024-03-11T11:07:37Z |
| publishDate | 2023-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Biological Research |
| spelling | doaj.art-8c7e3e02152c4b96b7c9a4f0992085392023-11-12T12:07:13ZengBMCBiological Research0717-62872023-11-015611810.1186/s40659-023-00463-0Chemogenetic inhibition of NTS astrocytes normalizes cardiac autonomic control and ameliorate hypertension during chronic intermittent hypoxiaKatherin Pereyra0Alexandra Las Heras1Camilo Toledo2Esteban Díaz-Jara3Rodrigo Iturriaga4Rodrigo Del Rio5Laboratory of Cardiorespiratory Control, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de ChileLaboratory of Cardiorespiratory Control, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de ChileLaboratory of Cardiorespiratory Control, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de ChileLaboratory of Cardiorespiratory Control, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de ChileLaboratory of Cardiorespiratory Control, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de ChileLaboratory of Cardiorespiratory Control, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de ChileAbstract Background Obstructive sleep apnea (OSA) is characterized by recurrent episodes of chronic intermittent hypoxia (CIH), which has been linked to the development of sympathoexcitation and hypertension. Furthermore, it has been shown that CIH induced inflammation and neuronal hyperactivation in the nucleus of the solitary tract (NTS), a key brainstem region involved in sympathetic and cardiovascular regulation. Since several studies have proposed that NTS astrocytes may mediate neuroinflammation, we aimed to determine the potential contribution of NTS-astrocytes on the pathogenesis of CIH-induced hypertension. Results Twenty-one days of CIH induced autonomic imbalance and hypertension in rats. Notably, acute chemogenetic inhibition (CNO) of medullary NTS astrocytes using Designer Receptors Exclusively Activated by Designers Drugs (DREADD) restored normal cardiac variability (LF/HF: 1.1 ± 0.2 vs. 2.4 ± 0.2 vs. 1.4 ± 0.3, Sham vs. CIH vs. CIH + CNO, respectively) and markedly reduced arterial blood pressure in rats exposed to CIH (MABP: 82.7 ± 1.2 vs. 104.8 ± 4.4 vs. 89.6 ± 0.9 mmHg, Sham vs. CIH vs. CIH + CNO, respectively). In addition, the potentiated sympathoexcitation elicit by acute hypoxic chemoreflex activation in rats exposed to CIH was also completely abolished by chemogenetic inhibition of NTS astrocytes using DREADDs. Conclusion Our results support a role for NTS astrocytes in the maintenance of heightened sympathetic drive and hypertension during chronic exposure to intermittent hypoxia mimicking OSA.https://doi.org/10.1186/s40659-023-00463-0Obstructive sleep apneaIntermittent hypoxiaAstrocytesNucleus of the solitary tractReactive astrocytesNeuroinflammation |
| spellingShingle | Katherin Pereyra Alexandra Las Heras Camilo Toledo Esteban Díaz-Jara Rodrigo Iturriaga Rodrigo Del Rio Chemogenetic inhibition of NTS astrocytes normalizes cardiac autonomic control and ameliorate hypertension during chronic intermittent hypoxia Biological Research Obstructive sleep apnea Intermittent hypoxia Astrocytes Nucleus of the solitary tract Reactive astrocytes Neuroinflammation |
| title | Chemogenetic inhibition of NTS astrocytes normalizes cardiac autonomic control and ameliorate hypertension during chronic intermittent hypoxia |
| title_full | Chemogenetic inhibition of NTS astrocytes normalizes cardiac autonomic control and ameliorate hypertension during chronic intermittent hypoxia |
| title_fullStr | Chemogenetic inhibition of NTS astrocytes normalizes cardiac autonomic control and ameliorate hypertension during chronic intermittent hypoxia |
| title_full_unstemmed | Chemogenetic inhibition of NTS astrocytes normalizes cardiac autonomic control and ameliorate hypertension during chronic intermittent hypoxia |
| title_short | Chemogenetic inhibition of NTS astrocytes normalizes cardiac autonomic control and ameliorate hypertension during chronic intermittent hypoxia |
| title_sort | chemogenetic inhibition of nts astrocytes normalizes cardiac autonomic control and ameliorate hypertension during chronic intermittent hypoxia |
| topic | Obstructive sleep apnea Intermittent hypoxia Astrocytes Nucleus of the solitary tract Reactive astrocytes Neuroinflammation |
| url | https://doi.org/10.1186/s40659-023-00463-0 |
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