doi: 10.1016/j.ijchy.2020.100048.
eCollection 2020 Dec.
Hypothesis: Unrecognized actions of ENaC blockade in improving refractory-resistant hypertension and residual cardiovascular risk
Affiliations
- PMID: 33447773
- PMCID: PMC7803029
- DOI: 10.1016/j.ijchy.2020.100048
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Hypothesis: Unrecognized actions of ENaC blockade in improving refractory-resistant hypertension and residual cardiovascular risk
Int J Cardiol Hypertens.
.
No abstract available
Keywords: Amiloride; Angiotensin II; ENaC; Epoxyeicosatrienoic acids; Immunity in hypertension; Resistant hypertension; Sodium.
Figures
Pathways of involvement of the epithelial sodium channel (ENaC) in the kidney and in dendritic cells (DC). #1 and #2 depict angiotensin II (AngII)-dependent (#1) and independent (#2) aldosterone (Aldo)-stimulation of renal ENaC. “Other” stands for non-AngII stimuli of aldosterone, represented graphically by an adipocyte in view of the putative existence of adipocyte secretagogues for aldosterone production by the adrenal gland. #3 shows aldosterone-independent activation of renal ENaC by a deficiency of epoxyeicosatrienoic acids (EET), as discussed in the text. #4 and #5 represent the consequence of salt or AngII activation of DC ENaC. #4 depicts renal ENaC stimulation by T-cell infiltration of the kidney, via direct effects of cytokines on the channel and also via generation of local, renal AngII. #5 depicts the tissue-damaging effects of activation of the DC ENaC channel, mediated by the inflammatory, oxidative and pro-fibrotic effects on renal and vascular tissues. These may account for the inflammation-dependent residual cardiovascular (CV) risk of treated hypertensive subjects. The symbols next to each pathway number represent the drug(s) that may interrupt them. ∗ = spironolactone for the treatment of hypertension, † = amiloride for the treatment of hypertension, and †† = amiloride for the treatment of residual CV risk. SKG1 = serum and glucocorticoid-regulated kinase, isoLG = isolevuglandins, ROS = reactive oxygen species, MPs = metalloproteinases.
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