Aldosterone Synthase Inhibitor Ameliorates Angiotensin II–Induced Organ Damage

• DOI: 10.1161/circulationaha.104.521625
• Publication Date: 2005-06-07T00:25:45Z
• Authors: Anette Fiebeler; Jürg Nussberger; Erdenechimeg Shag...; Song Rong; Georg Hilfenhaus; Nidal Al-Saadi; Ralf Dechend; Maren Wellner; Silke Meiners; Christiane Maser-...; Arco Y. Jeng; Randy L. Webb; Friedrich C. Luft; Dominik N. Muller
• Keywords: Aldosterone synthase

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. concentrations depend on activity of synthase (CYP11B2). We tested hypothesis that reducing by inhibiting CYP11B2 or adrenalectomy (ADX) ameliorate Furthermore, we investigated how much originates from adrenal gland. Methods Results— effect inhibitor FAD286, losartan, consequences ADX transgenic rats overexpressing human renin angiotensinogen genes (dTGR). dTGR-ADX received dexamethasone 1% salt. Dexamethasone-treated dTGR-salt served as a control group protocol. Untreated dTGR developed hypertension renal damage had 40% mortality rate (5/13) at 7 weeks. FAD286 reduced to 10% (1/10) ameliorated hypertrophy, albuminuria, cell infiltration, matrix deposition heart kidney. no blood pressure weeks 5 6 but slightly week7 (177±6 mm Hg dTGR+FAD286 200±5 dTGR). Losartan normalized during entire study. levels were losartan-treated dTGR. combined with salt treatment decreased circulating barely detectable levels. At week 7, ADX-dTGR-dexamethasone-salt 22% compared 73% dTGR-dexamethasone-salt. Both groups similarly hypertensive (190±9 187±4 Hg). In contrast, hypertrophy index, significantly after ( P <0.05). Conclusions— plays key role pathogenesis Ang II–induced The present results show adrenals main source aldosterone.