The epithelial sodium channel in inflammation and blood pressure modulation
A major regulator of blood pressure and volume homeostasis in the kidney is the epithelial sodium channel (ENaC). ENaC is composed of alpha(α)/beta(β)/gamma(γ) or delta(δ)/beta(β)/gamma(γ) subunits. The δ subunit is functional in the guinea pig, but not in routinely used experimental rodent models i...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-04-01
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| Series: | Frontiers in Cardiovascular Medicine |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2023.1130148/full |
| _version_ | 1797847905985363968 |
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| author | Taseer Ahmad Taseer Ahmad Lale A. Ertuglu Sepiso K. Masenga Thomas R. Kleyman Thomas R. Kleyman Thomas R. Kleyman Annet Kirabo |
| author_facet | Taseer Ahmad Taseer Ahmad Lale A. Ertuglu Sepiso K. Masenga Thomas R. Kleyman Thomas R. Kleyman Thomas R. Kleyman Annet Kirabo |
| author_sort | Taseer Ahmad |
| collection | DOAJ |
| description | A major regulator of blood pressure and volume homeostasis in the kidney is the epithelial sodium channel (ENaC). ENaC is composed of alpha(α)/beta(β)/gamma(γ) or delta(δ)/beta(β)/gamma(γ) subunits. The δ subunit is functional in the guinea pig, but not in routinely used experimental rodent models including rat or mouse, and thus remains the least understood of the four subunits. While the δ subunit is poorly expressed in the human kidney, we recently found that its gene variants are associated with blood pressure and kidney function. The δ subunit is expressed in the human vasculature where it may influence vascular function. Moreover, we recently found that the δ subunit is also expressed human antigen presenting cells (APCs). Our studies indicate that extracellular Na+ enters APCs via ENaC leading to inflammation and salt-induced hypertension. In this review, we highlight recent findings on the role of extra-renal ENaC in inflammation, vascular dysfunction, and blood pressure modulation. Targeting extra-renal ENaC may provide new drug therapies for salt-induced hypertension. |
| first_indexed | 2024-04-09T18:18:51Z |
| format | Article |
| id | doaj.art-67a864c59c304fd79f51acbfc452eeb8 |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-04-09T18:18:51Z |
| publishDate | 2023-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-67a864c59c304fd79f51acbfc452eeb82023-04-12T13:02:59ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2023-04-011010.3389/fcvm.2023.11301481130148The epithelial sodium channel in inflammation and blood pressure modulationTaseer Ahmad0Taseer Ahmad1Lale A. Ertuglu2Sepiso K. Masenga3Thomas R. Kleyman4Thomas R. Kleyman5Thomas R. Kleyman6Annet Kirabo7Department of Pharmacology, College of Pharmacy, University of Sargodha, Sargodha, PakistanDivision of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United StatesDivision of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United StatesDepartment of Physiological Sciences, School of Medicine and Health Sciences, Mulungushi University, Livingstone, ZambiaDepartment of Medicine, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Cell Biology, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, United StatesDivision of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United StatesA major regulator of blood pressure and volume homeostasis in the kidney is the epithelial sodium channel (ENaC). ENaC is composed of alpha(α)/beta(β)/gamma(γ) or delta(δ)/beta(β)/gamma(γ) subunits. The δ subunit is functional in the guinea pig, but not in routinely used experimental rodent models including rat or mouse, and thus remains the least understood of the four subunits. While the δ subunit is poorly expressed in the human kidney, we recently found that its gene variants are associated with blood pressure and kidney function. The δ subunit is expressed in the human vasculature where it may influence vascular function. Moreover, we recently found that the δ subunit is also expressed human antigen presenting cells (APCs). Our studies indicate that extracellular Na+ enters APCs via ENaC leading to inflammation and salt-induced hypertension. In this review, we highlight recent findings on the role of extra-renal ENaC in inflammation, vascular dysfunction, and blood pressure modulation. Targeting extra-renal ENaC may provide new drug therapies for salt-induced hypertension.https://www.frontiersin.org/articles/10.3389/fcvm.2023.1130148/fullepithelial sodium channel (ENaC)δ-ENaCantigen presenting cellsinflammationendothelium dysfunctionblood pressure |
| spellingShingle | Taseer Ahmad Taseer Ahmad Lale A. Ertuglu Sepiso K. Masenga Thomas R. Kleyman Thomas R. Kleyman Thomas R. Kleyman Annet Kirabo The epithelial sodium channel in inflammation and blood pressure modulation Frontiers in Cardiovascular Medicine epithelial sodium channel (ENaC) δ-ENaC antigen presenting cells inflammation endothelium dysfunction blood pressure |
| title | The epithelial sodium channel in inflammation and blood pressure modulation |
| title_full | The epithelial sodium channel in inflammation and blood pressure modulation |
| title_fullStr | The epithelial sodium channel in inflammation and blood pressure modulation |
| title_full_unstemmed | The epithelial sodium channel in inflammation and blood pressure modulation |
| title_short | The epithelial sodium channel in inflammation and blood pressure modulation |
| title_sort | epithelial sodium channel in inflammation and blood pressure modulation |
| topic | epithelial sodium channel (ENaC) δ-ENaC antigen presenting cells inflammation endothelium dysfunction blood pressure |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2023.1130148/full |
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