Arterial Hypertension. Consume Carbon Monoxide?
Epithelial sodium channels (ENaC) are generally responsible for the passive movement of sodium ions through the apical cell membrane of salt absorbing epithelia. Canonical ENaC is composed of three homologous subunits, most commonly being a combination of alpha, beta, and gamma subunits (αβɣ-ENaC). However, in humans, ENaC has also been found to exist as a combination of delta, beta, and gamma subunits (δβɣ-ENaC). ENaC subunits were also detected in the endothelium of arteries where they are exposed to shear stress from the blood flow. αβɣ-ENaC is known to be activated by shear stress and inhibit vascular relaxation potentially exacerbating the effects of hypertension. A potential new treatment option for hypertension is targeting arterial ENaC through carbon monoxide (CO). CO has been tested as an emerging potential treatment for cardiovascular disease and hypertension. Studies have shown conflicting effects of CO on αβɣ-ENaC activity. Currently the effect of CO on δβɣ-ENaC have been characterized, and how the effect of shear stress compared between αβγ-ENaC and δβγ-ENaC. Therefore, I aimed to use Two Electrode Voltage Clamping (TEVC) and Xenopus laevis oocytes expressing αβɣ-ENaC or δβɣ-ENaC, to examine how both types of ENaCs respond to shear stress and CO. Our data shows δβɣ-ENaC responds to shear stress in a dose dependent manner that is less sensitive compared to the response seen in αβɣ-ENaC. This suggests δβɣ-ENaC may potentially play a role in hypertension, but further experimentation is needed to confirm if it influences vascular relaxation like αβɣ-ENaC. Furthermore, no significant response was seen by both ENaCs towards carbon monoxide, but a strong biphasic trend was noted in δβɣ-ENaC that was not seen in αβɣ-ENaC. This suggests that carbon monoxide has potential in modulating αβɣ-ENaC activity that is based on concentration. Further experimentation to confirm this trend may place carbon monoxide as a potential therapeutic in the treatment of hypertension as well as explaining the conflicting results seen in literature as of currently.
Advisor: Fronius, Martin
Degree Name: Bachelor of Biomedical Sciences with Honours
Degree Discipline: Physiology
Publisher: University of Otago
Keywords: New Zealand; ENaC; Carbon Monoxide; Xenopus Oocytes; Hypertension; TEVC
Research Type: Thesis