gms | German Medical Science

28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

24. bis 27.11.2004, Hannover

Expression of endothelial and inducible nitric oxide synthase in diabetes mellitus: AT1 receptor antagonism vs. beta blockade

Expression der endothelialen und induzierbaren NO-Synthase bei Diabetes mellitus: AT1 Rezeptorantagonismus vs. Beta-Blockade

Meeting Abstract (Hypertonie 2004)

  • presenting/speaker M. Dorenkamp - Charité Universitätsmedizin Berlin (Berlin, D)
  • presenting/speaker A. Riad - Heart Center Leipzig, University Leipzig (Leipzig, D)
  • presenting/speaker S. Stiehl - Heart Center Leipzig, University Leipzig (Leipzig, D)
  • presenting/speaker D. Westermann - Heart Center Leipzig, University Leipzig (Leipzig, D)
  • presenting/speaker H.-P. Schultheiss - Charité - Universitätsmedizin Berlin (Berlin, D)
  • presenting/speaker V. Adams - Charité - Universitätsmedizin Berlin (Berlin, D)
  • presenting/speaker C. Tschöpe - Charité - Universitätsmedizin Berlin (Berlin, D)

Hypertonie 2004. 28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Hannover, 24.-27.11.2004. Düsseldorf, Köln: German Medical Science; 2005. Doc04hochP50

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/hoch2004/04hoch050.shtml

Veröffentlicht: 10. August 2005

© 2005 Dorenkamp 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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In diabetes mellitus (DM), nitric oxide synthases (NOS) are sources of enhanced oxidative stress, which in turn leads to cardiovascular dysfunction. We determined effects of treatment with an angiotensin type-1 receptor antagonist (AT1A) and a beta blocker (BB). Experiments were performed in streptozotocin (STZ)-induced diabetic Sprague Dawley (SD) rats treated with the AT1A candesartan (Can) (1.5mg/kg/d), or the BB metoprolol (Met) (30mg/kg/d) or vehicle and in age matched controls (n=9/group). Endothelial NOS (eNOS) mRNA (real-time PCR) and protein expression and inducible NOS (iNOS) protein expression (immunohistochemistry) were quantified in rat quadriceps musculature. Function of the inherent vascular bed was measured in vivo in the autoperfused hindlimb by injection of Krebs-Henseleit solution (200µl/kg) and of sodium nitroprusside (SNP, 40µg/kg). Increased expression of eNOS (mRNA: 0.43+/-0.18 vs. 23.1+/-13.4; protein: 0.54+/-0.09 vs. 2.81+/-0.37; p<0.05) and iNOS (protein: 1.27+/-0.17 vs. 5.24+/-0.13; p<0.05) displayed increased levels of oxidative stress in diabetic rats when compared with non-diabetic controls. In addition, DM was associated with severe impairment of endothelium-dependent and -independent vascular function. Both alterations in eNOS (mRNA: 0.04+/-0.02 vs. 23.1+/-13.4; protein: 0.93+/-0.19 vs. 2.81+/-0.37 and iNOS (1.45+/-0.45 vs. 5.24+/-0.13; p<0.05) expression and endothelial function (pressure amplitude: 38.9+/-3.1 vs. 22.9+/-1.9 mmHg; integral: 1844+/-160 vs. 1093+/-83 mmHg*s; p<0.05) were nearly reversed by AT1A as compared to vehicle-treated STZ-diabetic rats. BB whether altered eNOS or iNOS expression nor improved vascular function under diabetic conditions. Our findings indicate that AT1 receptor activation is crucial for the maintenance of pathologic vascular alterations during DM, and that their blockade is of therapeutic advantage.