AI Article Synopsis
- Inhibiting aldosterone synthase (CYP11B2) with FAD286 could be a new treatment to counteract the negative effects of aldosterone, which is important for managing conditions like hypertension.
- FAD286 was shown to effectively reduce aldosterone production in stimulated adrenocortical cells but had limited selectivity, also decreasing levels of other hormones like corticosterone and cortisol at higher doses.
- Overall, while FAD286 reduces angiotensin II-stimulated aldosterone levels, it also affects other steroid hormones, suggesting that its use may come with broader hormonal effects than initially intended.
Article Abstract
Inhibition of aldosterone synthase (CYP11B2) is an alternative treatment option to mineralocorticoid receptor antagonism to prevent harmful aldosterone effects. FAD286 is the best characterized aldosterone synthase inhibitor. However, to date, no study has used sensitive liquid chromatography-tandem mass spectrometry to characterize in detail the effect of FAD286 on the secreted steroid hormone profile of adrenocortical cells. Basal aldosterone production in NCI-H295R cells was detectable and 9-fold elevated after stimulation with angiotensin II. FAD286 inhibited this increase, showing a maximal effect at 10 nmol/l. Higher concentrations of FAD286 did not further reduce aldosterone concentrations, but showed a parallel reduction in corticosterone, cortisol and cortisone levels, reflecting additional inhibition of steroid-11β-hydroxylase (CYP11B1). Pregnenolone, progesterone and 17-OH-progesterone levels remained unaffected. In conclusion, the aldosterone synthase inhibitor FAD286 lowers angiotensin II-induced aldosterone concentrations in adrenocortical cells but the relative lack of selectivity over CYP11B1 is evident at higher FAD286 concentrations.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1055/s-0043-113829 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Mineralocorticoid axis activity and cardiac remodeling in patients with ACTH dependent Cushing's syndrome.
Endocr Connect
January 2025
P Kamenický, Centre de Référence des Maladies Rares de l'Hypophyse, Le Kremlin-Bicêtre, 94275, France.
Background: Arterial hypertension and left ventricular hypertrophy and remodeling are independent cardiovascular risk factors in patients with Cushing's syndrome. Changes in the renin-angiotensin system and in the mineralocorticoid axis activity could be involved as potential mechanisms in their pathogenesis, in addition to cortisol excess.
Methods: In this ancillary study of our previous study prospectively investigating patients with ACTH-dependent Cushing's syndrome by cardiac magnetic resonance imaging (NCT02202902), 11 patients without any interfering medication were cross-sectionally compared to 20 control subjects matched for age, sex and body mass index.
Irbesartan May Ameliorate Ventricular Remodeling by Inhibiting CREB-Mediated Cardiac Aldosterone Synthesis in Rats with Myocardial Infarction.
Int J Mol Sci
December 2024
Department of Cardiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510800, China.
Irbesartan improves ventricular remodeling (VR) following myocardial infarction (MI). This study investigates whether irbesartan attenuates VR by reducing aldosterone production in the heart and its underlying mechanisms. MI was induced in male Sprague-Dawley rats through coronary artery ligation.
View Article and Find Full Text PDFThe Effects of Aldosterone on Hypertension-Associated Kidney Injury in a Tg-hAS Mouse Model.
Biology (Basel)
December 2024
Department of Neurology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Hypertension remains a global health challenge due to its high prevalence and association with premature morbidity and mortality. Aldosterone, a mineralocorticoid hormone, and its receptor, the mineralocorticoid receptor (MR), are highly implicated in hypertension pathogenesis. Aldosterone synthase is the sole enzyme responsible for producing aldosterone in humans.
View Article and Find Full Text PDFClinical Pharmacokinetics and Pharmacodynamics of Baxdrostat.
Am J Cardiovasc Drugs
December 2024
East Coast Institute for Research, 3550 University Blvd S #101, Jacksonville, FL, USA.
Patients with hypertension are at an increased risk of cardiovascular disease and death. Resistant hypertension, or hypertension that is unsuccessfully treated with multiple antihypertensive medications, further exacerbates the complications and negative outcomes for patients. A new pathway, via aldosterone synthesis inhibition, is currently being studied as a method to reduce blood pressure values in patients who are currently taking other antihypertensive medications.
View Article and Find Full Text PDFE3 ubiquitin ligase TRIM2 identified as a novel suppressor of CYP11B2 and aldosterone production.
Cell Mol Life Sci
December 2024
Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.
Aldosterone-producing adenoma (APA) is a leading cause of primary aldosteronism (PA), a condition marked by excessive aldosterone secretion. CYP11B2, the aldosterone synthase, plays a critical role in aldosterone biosynthesis and the development of APA. Despite its significance, encoding regulatory mechanisms governing CYP11B2, particularly its degradation, remain poorly understood.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!