Epithelial Na+ Channel (ENaC) in Human Arteries – An Emerging Player in Hypertension

Abstract

The epithelial sodium channel (ENaC) in the kidney plays a key role in blood pressure regulation. Recent evidence from animal models indicates the expression of ENaC in vascular cells and suggests a role in the regulation of vascular tone and hypertension. However, it is unknown if ENaC is expressed in human arteries and if ENaC contributes to hypertension. The role of vascular ENaC in human hypertension may be further complicated by the existence of a fourth ENaC subunit δ, which is not expressed in rodents.In this study we aimed to characterise the expression of ENaC subunits in human arteries and to compare the expression of ENaC subunits in arteries from both normotensive and hypertensive patients. Human internal mammary arteries (HIMA) and human aortic punches from patients undergoing coronary artery bypass graft (CABG) surgery were collected through the HeartOtago network. The patients were divided into 3 groups on the basis of their medical history and recent blood pressure measurement: 1) Normotensive 2) Uncontrolled hypertensive and 3) Controlled hypertensive. The mRNA and protein expression of ENaC (α, β, γ and δ) were analysed with qPCR and western blot techniques respectively.We report for the first time that all four ENaC subunits are expressed at mRNA and protein levels in human arteries. In HIMA of the controlled hypertensive patients δ‐ENaC mRNA and protein expression were significantly decreased compared to normotensive patients and uncontrolled hypertensive patients (P<0.05), whereas, there was no significant difference observed between the normotensive and uncontrolled hypertensive groups. However, there were no changes in α‐, β‐ and γ‐ENaC between all 3 groups. In human aortic punches, there was a significant decrease in both β‐ (p<0.05) and γ‐ENaC (p<0.01) protein expression in controlled hypertensive patients compared to uncontrolled hypertensive and normotensive patients respectively.In summary, we observed downregulation of vascular ENaC subunits in controlled hypertensive patients compared to normotensive patients and uncontrolled hypertensive patients. Overall, our data provide new links between vascular ENaC expression and hypertension in human arteries.Support or Funding InformationDepartment of Physiology Doctoral Scholarship, University of Otago