Epithelial Sodium Channel δ Subunit Is Expressed in Human Arteries and Has Potential Association With Hypertension.


Journal

Hypertension (Dallas, Tex. : 1979)
ISSN: 1524-4563
Titre abrégé: Hypertension
Pays: United States
ID NLM: 7906255

Informations de publication

Date de publication:
07 2022
Historique:
pubmed: 6 5 2022
medline: 11 6 2022
entrez: 5 5 2022
Statut: ppublish

Résumé

Elevated expression and increased activity of vascular epithelial sodium channel (ENaC) can result in vascular dysfunction in small animal models. However, there is limited or no knowledge on expression and function of ENaC channels in human vasculature. Hence, this study explored the expression and function of ENaC in human arteries and their association with hypertension. Human internal mammary artery (IMA) and aorta were obtained from cardiovascular patients undergoing coronary artery bypass graft surgery. Expression of the ENaC subunit was analyzed by polymerase chain reaction, Western blot, and immunohistochemistry. ENaC function was observed by patch-clamp electrophysiology in endothelial cells isolated from IMA. Levels of ENaC subunit expression levels were compared between arteries from normotensive, uncontrolled hypertensive, and controlled hypertensive patients. For the first time, expression of α, β, γ, and δ was detected at mRNA and protein levels in human IMA and aorta. Single-channel patch-clamp recordings identified both αβγ- and δβγ-like channel conductance in primary endothelial cells isolated and cultured from IMA. Reduced expression of the δ subunit was observed in controlled hypertensive IMA, whereas reduced expression of γ-ENaC was observed in controlled hypertensive aorta. These data suggest that functional ENaC channels are expressed in human arteries and their expression levels are associated with hypertension.

Sections du résumé

BACKGROUND
Elevated expression and increased activity of vascular epithelial sodium channel (ENaC) can result in vascular dysfunction in small animal models. However, there is limited or no knowledge on expression and function of ENaC channels in human vasculature. Hence, this study explored the expression and function of ENaC in human arteries and their association with hypertension.
METHODS
Human internal mammary artery (IMA) and aorta were obtained from cardiovascular patients undergoing coronary artery bypass graft surgery. Expression of the ENaC subunit was analyzed by polymerase chain reaction, Western blot, and immunohistochemistry. ENaC function was observed by patch-clamp electrophysiology in endothelial cells isolated from IMA. Levels of ENaC subunit expression levels were compared between arteries from normotensive, uncontrolled hypertensive, and controlled hypertensive patients.
RESULTS
For the first time, expression of α, β, γ, and δ was detected at mRNA and protein levels in human IMA and aorta. Single-channel patch-clamp recordings identified both αβγ- and δβγ-like channel conductance in primary endothelial cells isolated and cultured from IMA. Reduced expression of the δ subunit was observed in controlled hypertensive IMA, whereas reduced expression of γ-ENaC was observed in controlled hypertensive aorta.
CONCLUSIONS
These data suggest that functional ENaC channels are expressed in human arteries and their expression levels are associated with hypertension.

Identifiants

pubmed: 35510563
doi: 10.1161/HYPERTENSIONAHA.122.18924
doi:

Substances chimiques

Epithelial Sodium Channels 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1385-1394

Auteurs

Puja Paudel (P)

Department of Physiology, School of Biomedical Sciences (P.P., I.v.H., F.J.M., M.F.), University of Otago, Dunedin, New Zealand.
HeartOtago (P.P., I.v.H., S.C., M.F.), University of Otago, Dunedin, New Zealand.

Isabelle van Hout (I)

Department of Physiology, School of Biomedical Sciences (P.P., I.v.H., F.J.M., M.F.), University of Otago, Dunedin, New Zealand.
HeartOtago (P.P., I.v.H., S.C., M.F.), University of Otago, Dunedin, New Zealand.

Richard W Bunton (RW)

Department of Cardiothoracic Surgery, Otago Medical School, Dunedin Hospital, New Zealand (R.W.B., D.J.P.).

Dominic J Parry (DJ)

Department of Cardiothoracic Surgery, Otago Medical School, Dunedin Hospital, New Zealand (R.W.B., D.J.P.).

Sean Coffey (S)

HeartOtago (P.P., I.v.H., S.C., M.F.), University of Otago, Dunedin, New Zealand.
Department of Medicine, Otago Medical School (S.C.), University of Otago, Dunedin, New Zealand.

Fiona J McDonald (FJ)

Department of Physiology, School of Biomedical Sciences (P.P., I.v.H., F.J.M., M.F.), University of Otago, Dunedin, New Zealand.

Martin Fronius (M)

Department of Physiology, School of Biomedical Sciences (P.P., I.v.H., F.J.M., M.F.), University of Otago, Dunedin, New Zealand.
HeartOtago (P.P., I.v.H., S.C., M.F.), University of Otago, Dunedin, New Zealand.

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