Mineralocorticoid antagonists and ENaC inhibitors in hyperaldosteronism

Hill, Michael A.; Sowers, James R.

doi:10.1111/jch.13566

Cited by 6 publications

(3 citation statements)

References 17 publications

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“…83 Although this mechanism has not been described in the context of SSBP, compelling evidence indicates that aldosterone-induced endothelial MR activation increases EnNaC and promotes EnNaC-mediated endothelial and vascular stiffness in female mice. [84][85][86] Therefore, one could speculate that the aldosterone-MR-EnNAC axis activation in female vasculature predisposes to SSBP predominantly rather than shifting in the pressure natriuresis curve.…”

Section: Salt-sensitive Renal Pressure Natriuresis Is Blunted In Femalesmentioning

confidence: 99%

Salt Sensitivity of Blood Pressure in Women

2023

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Several clinical and large population studies indicate that women are more salt-sensitive than men, yet the precise mechanisms by which the sexually dimorphic onset manifests remains incompletely understood. Here, we evaluate recent epidemiological data and highlight current knowledge from studies investigating sex-specific mechanisms of salt-sensitive blood pressure (SSBP). Emerging evidence indicates that women of all ethnicities are more salt-sensitive than men, at all ages both premenopausal and postmenopausal. However, menopause exacerbates severity and prevalence of SSBP, suggesting that female sex chromosomes predispose to and female sex hormones mitigate SSBP. Results from both human and rodent studies support the contribution of enhanced and inappropriate activation of the aldosterone-ECMR (endothelial cell mineralocorticoid receptor) axis promoting vascular dysfunction in females. Increases in adrenal response to angiotensin II, in association with higher ECMR expression and activation of endothelial ENaC (epithelial sodium channel) in females compared to males, are emerging as central players in the development of endothelial dysfunction and SSBP in females. Female sex increases the prevalence and susceptibility of SSBP and sex hormones and sex chromosome complement may exert antagonistic effects in the development of the female heightened SSBP.

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Section: Salt-sensitive Renal Pressure Natriuresis Is Blunted In Femalesmentioning

confidence: 99%

Salt Sensitivity of Blood Pressure in Women

2023

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“…It has also been reported that it controls the fertilization ability of sperm [51]. Salt-taste channels, epithelial sodium channels (ENaCs), are known to be expressed in the kidney, distal colon, bladder, stomach and lungs [52]. Almost every cell in the body expresses at least one member of the TRP channel family, which has distinct biophysical, mechanical, and pharmacological properties [53].…”

Section: Receptors Involved In Sensory Nutritionmentioning

confidence: 99%

Sensory Nutrition and Bitterness and Astringency of Polyphenols

Osakabe,

Shimizu,

Fujii

et al. 2024

Biomolecules

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Recent studies have demonstrated that the interaction of dietary constituents with taste and olfactory receptors and nociceptors expressed in the oral cavity, nasal cavity and gastrointestinal tract regulate homeostasis through activation of the neuroendocrine system. Polyphenols, of which 8000 have been identified to date, represent the greatest diversity of secondary metabolites in plants, most of which are bitter and some of them astringent. Epidemiological studies have shown that polyphenol intake contributes to maintaining and improving cardiovascular, cognitive and sensory health. However, because polyphenols have very low bioavailability, the mechanisms of their beneficial effects are unknown. In this review, we focused on the taste of polyphenols from the perspective of sensory nutrition, summarized the results of previous studies on their relationship with bioregulation and discussed their future potential.

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“… 18 , 19 In addition, epithelial sodium channel (ENaC) inhibitors have being considered as potential medical agents for hyperaldosteronism. 20 …”

Section: Introductionmentioning

confidence: 99%

Comparison of different medical treatments for primary hyperaldosteronism: a systematic review and network meta-analysis

Ho,

Hsiao,

et al. 2024

Therapeutic Advances in Chronic Disease

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Background: The effectiveness and side effects between different medical treatments in patients with primary hyperaldosteronism have not been systematically studied. Objective: To analyze the efficacy between different mineralocorticoid receptor antagonists (MRAs) and epithelial sodium channel (ENaC) inhibitors in a network meta-analysis (NMA) framework, while also evaluating adverse events. Design: Systematic review and NMA. Data sources and methods: The systematic review and NMA was reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, MEDLINE, the Cochrane library, and Excerpta Medica database (EMBASE) were searched for randomized controlled trials (RCTs) involving adult patients with primary hyperaldosteronism until 23 June 2023. Studies that compared the efficacy and side effects of different medical treatments of primary hyperaldosteronism were included. The primary outcomes included the effect on blood pressure, serum potassium, and major adverse cardiovascular events. The secondary outcomes were adverse events related to MRAs (hyperkalemia and gynecomastia). Frequentist NMA and pairwise meta-analysis were conducted. Results: A total of 5 RCTs comprising 392 participants were included. Eplerenone, esaxerenone, and amiloride were compared to spironolactone and demonstrated comparable effect on the reduction of systolic blood pressure. In comparison to spironolactone, eplerenone exhibited a less pronounced effect on reducing diastolic blood pressure [−4.63 mmHg; 95% confidence interval (CI): −8.87 to −0.40 mmHg] and correcting serum potassium (−0.2 mg/dL; 95% CI: −0.37 to −0.03 mg/dL). Spironolactone presented a higher risk of gynecomastia compared with eplerenone (relative risk: 4.69; 95% CI: 3.58–6.14). Conclusion: The present NMA indicated that the blood pressure reduction and potassium-correcting effects of the three MRAs may demonstrate marginal differences, with confidence levels in the evidence being very low. Therefore, further research is needed to explore the efficacy of these MRAs, especially regarding their impact on mortality and cardiovascular outcomes. Trial registration: PROSPERO (CRD: 42023446811).

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Mineralocorticoid antagonists and ENaC inhibitors in hyperaldosteronism

Cited by 6 publications

References 17 publications

Salt Sensitivity of Blood Pressure in Women

Salt Sensitivity of Blood Pressure in Women

Sensory Nutrition and Bitterness and Astringency of Polyphenols

Comparison of different medical treatments for primary hyperaldosteronism: a systematic review and network meta-analysis

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