gms | German Medical Science

28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

24. bis 27.11.2004, Hannover

Anti-inflammatory effects of rosuvastatin are dose-dependent: Prevention of leukocyte infiltration, iNOS induction and collagen expression in angiotensin II-induced nephrosclerosis

Anti-Entzündungseffekte von Rosuvastatin sind Dosis-abhängig: Hemmung von Leukozyteninfilatratio, iNOS-Induktion und Kollagen-Expression bei Angiotensin II-induzierter Nephrosklerose

Meeting Abstract (Hypertonie 2004)

  • J.-K. Park - Medizinische Hochschule Hannover (Hannover, D)
  • E.M.A. Mervaala - Insitute of Biomedicine, University of Helsinki (Helsinki, FIN)
  • D.N. Müller - Franz-Volhard-Klinik, Charité, Berlin (Berlin, D)
  • A. Fiebeler - Franz-Volhard-Klinik, Charité, Berlin (Berlin, D)
  • F.C. Luft - Franz-Volhard-Klinik, Charité, Berlin (Berlin, D)
  • H. Haller - Medizinische Hochschule Hannover (Hannover, D)

Hypertonie 2004. 28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Hannover, 24.-27.11.2004. Düsseldorf, Köln: German Medical Science; 2005. Doc04hochP52

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/hoch2004/04hoch052.shtml

Veröffentlicht: 10. August 2005

© 2005 Park 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

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Objectives: Recently, clinical trials have shown that statins are effective in preventing endorgan damage. However, the beneficial effects could not be fully explained on the basis of cholesterol reduction.

Methods: We have used an angiotensin II-dependent rat model of renal failure to test the hypothesis that a new HMG-CoA reductase inhibitor, rosuvastatin, influences leukocyte adhesion and infiltration, prevents induction of inducible NO sythase (iNOS) and ameliorates endorgan damage. In order to test whether these effects are dose-dependent, rat, transgenic for human renin and angiotensinogen (dTGR), were treated chronically, from age 4 to 7 weeks (n=10 per group), with 1, 10 and 50mg/kg rosuvastatin. Untreated dTGR developed moderate hypertension, cardiac hypertrophy and severs renal damage with focal necrosis, and a 100-fold increase in albuminuria.

Results: Mortality of untreated dTGR at the age of 7 weeks was 68%. Blood pressure was not affected by rosuvastain treatment. However, rosuvastain decreased mortality dose-dependently compared to untreated dTGR (to 43%, 20%, and 7% at 1, 10 and 50mg/kg respectively). Albuminuria was reduced dose-dependently and plasma creatine was also lower. Expression of the adhesion molecules ICAM-1 and VCAM_1 was markedly reduced by rosuvastatin treatment. Neutrophil and monocyte infiltration of the kidney was reduced almost completely at the highest dose. Immmunohistochemical analysis shownd an decreased iNOS expression by rosuvastatin treated dTGR. Immuoreactivity was stronger in the cortex than in the medulla.

Finally, expression of matrix proteins (type IV collagen, fibronectin) was also dose-dependently reduced by rosuvastatin treatment.

Conclusion: Rosuvastatin dose-dependentliy ameliorates angiotensin II-induced renal damage. The effect on renal cellar damage is independent of changes in systemic BP, and may be due to a reduction in renal inflammation and induction of iNOS expression.