Potential Therapeutic Use of Neurosteroids for Hypertension
The sympathetic nervous system (SNS) contribution to long-term setting of blood pressure (BP) and hence hypertension has been a continuing controversy over many decades. However, the contribution of increased sympathetic vasomotor tone to the heart, kidney, and blood vessels has been suggested as a...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-12-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphys.2019.01477/full |
| _version_ | 1818195810597208064 |
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| author | Geoffrey A. Head Kristy L. Jackson Cindy Gueguen |
| author_facet | Geoffrey A. Head Kristy L. Jackson Cindy Gueguen |
| author_sort | Geoffrey A. Head |
| collection | DOAJ |
| description | The sympathetic nervous system (SNS) contribution to long-term setting of blood pressure (BP) and hence hypertension has been a continuing controversy over many decades. However, the contribution of increased sympathetic vasomotor tone to the heart, kidney, and blood vessels has been suggested as a major influence on the development of high BP which affects 30–40% of the population. This is relevant to hypertension associated with chronic stress, being overweight or obese as well to chronic kidney disease. Treatments that have attempted to block the peripheral aspects of the SNS contribution have included surgery to cut the sympathetic nerves as well as agents to block α- and β-adrenoceptors. Other treatments, such as centrally acting drugs like clonidine, rilmenidine, or moxonidine, activate receptors within the ventrolateral medulla to reduce the vasomotor tone overall but have side effects that limit their use. None of these treatments target the cause of the enhanced sympathetic tone. Recently we have identified an antihypertensive action of the neurosteroid allopregnanolone in a mouse model of neurogenic hypertension. Allopregnanolone is known to facilitate high-affinity extra-synaptic γ-aminobutyric acid A receptors (GABAAR) through allosteric modulation and transcriptional upregulation. The antihypertensive effect was specific for increased expression of δ subunits in the amygdala and hypothalamus. This focused review examines the possibility that neurosteroids may be a novel therapeutic approach to address the neurogenic contribution to hypertension. We discuss the causes and prevalence of neurogenic hypertension, current therapeutic approaches, and the applicability of using neurosteroids as antihypertensive therapy. |
| first_indexed | 2024-12-12T01:24:06Z |
| format | Article |
| id | doaj.art-d3e226cf948e4c40afc6380efea72c3c |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-12T01:24:06Z |
| publishDate | 2019-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-d3e226cf948e4c40afc6380efea72c3c2022-12-22T00:43:09ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2019-12-011010.3389/fphys.2019.01477503127Potential Therapeutic Use of Neurosteroids for HypertensionGeoffrey A. HeadKristy L. JacksonCindy GueguenThe sympathetic nervous system (SNS) contribution to long-term setting of blood pressure (BP) and hence hypertension has been a continuing controversy over many decades. However, the contribution of increased sympathetic vasomotor tone to the heart, kidney, and blood vessels has been suggested as a major influence on the development of high BP which affects 30–40% of the population. This is relevant to hypertension associated with chronic stress, being overweight or obese as well to chronic kidney disease. Treatments that have attempted to block the peripheral aspects of the SNS contribution have included surgery to cut the sympathetic nerves as well as agents to block α- and β-adrenoceptors. Other treatments, such as centrally acting drugs like clonidine, rilmenidine, or moxonidine, activate receptors within the ventrolateral medulla to reduce the vasomotor tone overall but have side effects that limit their use. None of these treatments target the cause of the enhanced sympathetic tone. Recently we have identified an antihypertensive action of the neurosteroid allopregnanolone in a mouse model of neurogenic hypertension. Allopregnanolone is known to facilitate high-affinity extra-synaptic γ-aminobutyric acid A receptors (GABAAR) through allosteric modulation and transcriptional upregulation. The antihypertensive effect was specific for increased expression of δ subunits in the amygdala and hypothalamus. This focused review examines the possibility that neurosteroids may be a novel therapeutic approach to address the neurogenic contribution to hypertension. We discuss the causes and prevalence of neurogenic hypertension, current therapeutic approaches, and the applicability of using neurosteroids as antihypertensive therapy.https://www.frontiersin.org/article/10.3389/fphys.2019.01477/fullneurogenic hypertensionallopregnanoloneγ-aminobutyric acid receptor AamygdalahypothalamusSchlager mice |
| spellingShingle | Geoffrey A. Head Kristy L. Jackson Cindy Gueguen Potential Therapeutic Use of Neurosteroids for Hypertension Frontiers in Physiology neurogenic hypertension allopregnanolone γ-aminobutyric acid receptor A amygdala hypothalamus Schlager mice |
| title | Potential Therapeutic Use of Neurosteroids for Hypertension |
| title_full | Potential Therapeutic Use of Neurosteroids for Hypertension |
| title_fullStr | Potential Therapeutic Use of Neurosteroids for Hypertension |
| title_full_unstemmed | Potential Therapeutic Use of Neurosteroids for Hypertension |
| title_short | Potential Therapeutic Use of Neurosteroids for Hypertension |
| title_sort | potential therapeutic use of neurosteroids for hypertension |
| topic | neurogenic hypertension allopregnanolone γ-aminobutyric acid receptor A amygdala hypothalamus Schlager mice |
| url | https://www.frontiersin.org/article/10.3389/fphys.2019.01477/full |
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