Aldosterone Synthase Inhibitor Ameliorates Angiotensin II–Induced Organ Damage
- 14 June 2005
- journal article
- research article
- Published by Wolters Kluwer Health in Circulation
- Vol. 111 (23) , 3087-3094
- https://doi.org/10.1161/circulationaha.104.521625
Abstract
Background— Aldosterone and angiotensin (Ang) II both may cause organ damage. Circulating aldosterone is produced in the adrenals; however, local cardiac synthesis has been reported. Aldosterone concentrations depend on the activity of aldosterone synthase (CYP11B2). We tested the hypothesis that reducing aldosterone by inhibiting CYP11B2 or by adrenalectomy (ADX) may ameliorate organ damage. Furthermore, we investigated how much local cardiac aldosterone originates from the adrenal gland. Methods and Results— We investigated the effect of the CYP11B2 inhibitor FAD286, losartan, and the consequences of ADX in transgenic rats overexpressing both the human renin and angiotensinogen genes (dTGR). dTGR-ADX received dexamethasone and 1% salt. Dexamethasone-treated dTGR-salt served as a control group in the ADX protocol. Untreated dTGR developed hypertension and cardiac and renal damage and had a 40% mortality rate (5/13) at 7 weeks. FAD286 reduced mortality to 10% (1/10) and ameliorated cardiac hypertrophy, al...Keywords
This publication has 29 references indexed in Scilit:
- Mechanism for Aldosterone Potentiation of Angiotensin II–Stimulated Rat Arterial Smooth Muscle Cell ProliferationHypertension, 2004
- Aldosterone Potentiates Angiotensin II–Induced Signaling in Vascular Smooth Muscle CellsCirculation, 2004
- Aldosterone, Through Novel Signaling Proteins, Is a Fundamental Molecular Bridge Between the Genetic Defect and the Cardiac Phenotype of Hypertrophic CardiomyopathyCirculation, 2004
- Vascular synthesis of aldosterone: role in hypertensionMolecular and Cellular Endocrinology, 2004
- Immediate Administration of Mineralocorticoid Receptor Antagonist Spironolactone Prevents Post-Infarct Left Ventricular Remodeling Associated With Suppression of a Marker of Myocardial Collagen Synthesis in Patients With First Anterior Acute Myocardial InfarctionCirculation, 2003
- Eplerenone, a Selective Aldosterone Blocker, in Patients with Left Ventricular Dysfunction after Myocardial InfarctionNew England Journal of Medicine, 2003
- Human Epidermal Growth Factor Receptor-1 Expression Renders Chinese Hamster Ovary Cells Sensitive to Alternative Aldosterone SignalingJournal of Biological Chemistry, 2002
- The Effect of Spironolactone on Morbidity and Mortality in Patients with Severe Heart FailureNew England Journal of Medicine, 1999
- Dietary salt excess unmasks blunted aldosterone suppression and sodium retention in the stroke-prone phenotype of the spontaneously hypertensive ratJournal Of Hypertension, 1993
- Vascular angiotensin II receptors in renal and DOCA-salt hypertensive rats.Hypertension, 1983