gms | German Medical Science

28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

24. bis 27.11.2004, Hannover

Diabetic ETB Receptor Deficient Rats Develop Severe Hypertension and Pronounced Renal Pahtology

Diabetische ETB-Rezeptor-defiziente Ratten entwickeln schweren Bluthochdruck und verstärkte Nierenschädigung

Meeting Abstract (Hypertonie 2004)

  • T. Pfab - Center for Cardiovascular Research, Charité (Berlin, D)
  • C. Thöne-Reineke - Center for Cardiovascular Research, Charité (Berlin, D)
  • I. Lange - Center for Cardiovascular Research, Charité (Berlin, D)
  • C. M. Richter - Center for Cardiovascular Research, Charité (Berlin, D)
  • H. Witt - Center for Cardiovascular Research, Charité (Berlin, D)
  • P. Ruiz - Center for Cardiovascular Research, Charité (Berlin, D)
  • M. Yanagisawa - Howard Hughes Medical Institute, Texas
  • B. Hocher - Inselspital Bern (Bern, CH)

Hypertonie 2004. 28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Hannover, 24.-27.11.2004. Düsseldorf, Köln: German Medical Science; 2005. Doc04hochP15

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/hoch2004/04hoch015.shtml

Veröffentlicht: 10. August 2005

© 2005 Pfab 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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Background: Diabetic nephropathy is associated with enhanced renal synthesis of endothelin (ET)-1. Animal studies suggest beneficial effects of ET receptor antagonists on its progression.

Methods: To clarify the role of the ETB receptor 4 groups of male rats were investigated: (i) homozygous rescued ETB receptor deficient rats with streptozotocin-induced diabetes mellitus, (ii) ETB deficient controls, (iii) diabetic controls and (iv) healthy controls (n=10 per group). Blood pressure, heart rate, kidney function and serum parameters were regularly measured over 10 weeks and histological analyses carried out afterwards. Renal gene expression profiles were assessed by oligonucleotide array.

Results: As described previously ETB receptor deficient animals are hypertensive. After induction of diabetes there was a strong rise of blood pressure in ETB deficient rats, whereas it fell slightly in diabetic controls. Kidney function deteriorated faster in diabetic ETB deficient rats in accordance with morphological changes. Since ET via the ETB receptor activates eNOS we analysed urinary excretion of nitrate and cGMP. Excretion is elevated in diabetic ETB deficient rats. The oligonucleotide array revealed a number of differentially expressed transcripts. The genes of hypertension-associated protein and renin-1 are the ones that are most clearly upregulated in diabetic ETB deficient rats as compared to diabetic controls.

Conclusion: The study indicates that a complete knockout of renal and vascular ETB receptors in male rats with streptozotocin-induced diabetes mellitus results in severe hypertension. The pronounced structural and functional renal pathology in this group is probably secondary to hypertension. The strong rise of blood pressure is not caused by suppression of the NO system. The oligonucleotide array results suggest that an activation of the renin-angiotensin-aldosterone system is involved. ETB receptor antagonists might be harmful for diabetic individuals.