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. 2020 Sep 12:7:100048.
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

Fernando Elijovich  1 , Annet Kirabo  1 , Cheryl L Laffer  1
Affiliations

Hypothesis: Unrecognized actions of ENaC blockade in improving refractory-resistant hypertension and residual cardiovascular risk

Fernando Elijovich et al. Int J Cardiol Hypertens. .
No abstract available

Keywords: Amiloride; Angiotensin II; ENaC; Epoxyeicosatrienoic acids; Immunity in hypertension; Resistant hypertension; Sodium.

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Figures

Fig. 1
Fig. 1
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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