gms | German Medical Science

28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

24. bis 27.11.2004, Hannover

An Aldosterone Synthase Inhibitor Ameliorates Angiotensin II-induced End-Organ Damage

Meeting Abstract (Hypertonie 2004)

  • A. Fiebeler - Medical Faculty of the Charité, HELIOS Klinikum-Berlin, Franz Volhard Clinic
  • J. Nussberger - Centre Hospitalier Universitaire Vaudois, Hypertension Division, Lausanne, Switzerland
  • E. Shagdarsuren - Medical Faculty of the Charité, HELIOS Klinikum-Berlin, Franz Volhard Clinic
  • S. Rong - Medical School of Hannover (Hannover, D)
  • G. Hilfenhaus - Medical School of Hannover (Hannover, D)
  • N. Al-Saadi - Medical Faculty of the Charité, HELIOS klinikum-Berlin, Franz Volhard Clinic
  • R. Dechend - Medical Faculty of the Charité, HELIOS klinikum-Berlin, Franz Volhard Clinic
  • M. Wellner - Medical Faculty of the Charité, HELIOS klinikum-Berlin, Franz Volhard Clinic
  • S. Meiners - Medical Faculty of the Charité, HELIOS klinikum-Berlin, Franz Volhard Clinic
  • C. Maser-Gluth - University of Heidelberg, Insitute of Pharmacology (Heidelberg, D)
  • A. Jeng - Novartis Pharmaceuticals Ltd., East Hanover, New Jersey, USA
  • R. Webb - Novartis Pharmaceuticals Ltd., East Hanover, New Jersey, USA
  • F. Luft - Medical Faculty of the Charité, HELIOS Klinikum-Berlin, Franz Volhard Clinic, Max Delbrück Center for Molecular Mecine (Berlin-Buch, D)
  • D. Müller - Medical Faculty of the Charité, HELIOS Klinikum-Berlin, Franz Volhard Clinic, Max Delbrück Center for Molecular Mecine (Berlin-Buch, D)

Hypertonie 2004. 28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Hannover, 24.-27.11.2004. Düsseldorf, Köln: German Medical Science; 2005. Doc04hochP65

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/hoch2004/04hoch065.shtml

Veröffentlicht: 10. August 2005

© 2005 Fiebeler et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Background: Aldosterone (Ald) and angiotensin (Ang) II both cause end-organ damage. Ald is mainly produced in the adrenals; however, local cardiac synthesis has been reported. Ald concentrations depend on Ald synthase (CYP11B2). We tested the hypothesis that removing Ald by inhibiting Cyp11B2 or by adrenalectomy ameliorates end-organ damage. Furthermore, we investigated whether or not local cardiac Ald is adrenal gland-dependent.

Method: We investigated the CYP11B2 inhibitor FAD286 and the consequences of adrenalectomy (ADX) in transgenic rats overexpressing both the human renin and angiotensinogen genes (dTGR). dTGR-ADX received dexamethasone and 1% salt. dTGR-salt served as control group in the ADX protocol.

Results: Untreated dTGR developed hypertension, cardiac, and renal damage and a 40% mortality (5/13) at 7 weeks. FAD286 reduced mortality to 10% (1/10), ameliorated cardiac hypertrophy, albuminuria, cell infiltration, and matrix deposition in heart and kidney. FAD286 had a minor effect on BP (177±6 mm Hg), compared to dTGR (200±5 mm Hg; p<0.05). Circulating and cardiac Ald levels were reduced in FAD286 and Los-treated dTGR. Adrenalectomy decreased circulating and cardiac Ald to barely detectable levels. At week 7, ADX-dTGR-salt had a 22% mortality compared to 73% in dTGR-salt. Both groups were similarly hypertensive (190±9 vs. 187±4 mm Hg). In contrast, cardiac hypertrophy index, albuminuria, cell, and matrix deposition were significantly reduced after ADX (p<0.05).

Conclusion: FAD286 ameliorates Ang II-induced renal and cardiac damage. Ald plays a key role in the pathogenesis of Ang II-induced end-organ damage. The Ald produced in the adrenals is main source for cardiac Ald.