gms | German Medical Science

27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

Deutsche Liga zur Bekämpfung des hohen Blutdrucks – Deutsche Hypertonie Gesellschaft e. V.

26. bis 29.11.2003, Bonn

End Organ Damage in Transgenic Rats with Ang II-Dependent Hypertension Involves Local Formation of Advanced Glycation End Products (AGEs)

Die Rolle von glykierten Proteinen (AGEs) für die Entstehung von Ang II-abhängigen Endorganschäden

Meeting Abstract (Hypertonie 2003)

Suche in Medline nach

  • presenting/speaker J. Bohlender - Klinik für Innere Medizin III (Jena, D)
  • S. Franke - Klinik für Innere Medizin III (Jena, D)
  • G. Stein - Klinik für Innere Medizin III (Jena, D)

Hypertonie 2003. 27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Bonn, 26.-29.11.2003. Düsseldorf, Köln: German Medical Science; 2004. Doc03hochP95

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/hoch2003/03hoch195.shtml

Veröffentlicht: 11. November 2004

© 2004 Bohlender 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

Aims

Advanced glycation end products (AGEs) have been associated with chronic renal insufficiency and cytokine-mediated proinflammatory states. AGEs may produce protein crosslinks with tissue stiffening and induce receptor-mediated proinflammatory responses with cellular dysfunction. Their role in angiotensin-induced glomerular and vascular damage, however, remains unclear.

Methods

We examined kidneys, hearts, and aortas from rats, double transgenic for human angiotensinogen and renin (TGR) aged 3 months and nontransgenic controls (CTR) by immuno-histochemical staining for N-omega-(carboxymehtyl)-lysine (CML), NFkappaB. CML and pentosidine-modified proteins in plasma were measured by ELISA and HPLC (n=8 per group). Blood pressure was measured by tail-cuff.

Results

Systolic blood pressure was >180 mm Hg in TGR and 115-130 mm Hg in CTR. TGR showed avid staining for CML in glomeruli while glomerular and interstitial inflammatory damage and fibrosis was detected. NFkappaB was locally activated. Collecting duct epithe-lium, endothelium of renal and coronary arteries similarly showed CMl staining. Aortic walls showed a weaker patchy staining of the smooth muscle cell layers and interstitial matrix respetively. Adjacent tissue did not stain for CML nor did tissues from CTR. Plasma CML was about 15% higher in TGR vs. CTR (p<0.05), whereas pentosidine concentrations were below the assay sensitivity in both TGR and CTR.

Conclusion

We here demonstrate for the first time local formation and accumulation of AGEs in glomeruli and arteries in rats with transgenic, angiotensin-induced hypertension and endorgan damage. The AGEs may induce local inflammation by activation of RAGE, their receptor, and NFkappaB-dependent intracellular pathways thereby promoting glomerular and vascular damage and fibrosis.