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Related Experiment Videos

Chronic vasopeptidase inhibition normalizes diabetic endothelial dysfunction.

Stefan Schäfer1, Kerstin Steioff, Wolfgang Linz

  • 1Disease Group Cardiovascular Diseases, Building H 821, Aventis Pharma Deutschland GmbH, D-65926 Frankfurt am Main, Germany. stefan.schaefer@aventis.com

European Journal of Pharmacology
|January 28, 2004
PubMed
Summary
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Type 2 diabetes mellitus causes vascular issues. In Zucker diabetic fatty rats, vasopeptidase inhibition with AVE7688 normalized blood vessel function, suggesting it may prevent diabetes-related vascular complications.

Area of Science:

  • Cardiovascular Science
  • Endocrinology
  • Pharmacology

Background:

  • Type 2 diabetes mellitus (T2DM) is a significant contributor to vascular morbidity.
  • Animal models are crucial for understanding T2DM's vascular complications, but require thorough characterization.
  • Endothelial dysfunction is a key pathological feature in T2DM vascular disease.

Purpose of the Study:

  • To characterize endothelial function in the Zucker diabetic fatty (ZDF) rat model of T2DM.
  • To investigate the therapeutic potential of vasopeptidase inhibition in mitigating T2DM-induced endothelial dysfunction.

Main Methods:

  • Utilized the Zucker diabetic fatty (ZDF) rat as an animal model for type 2 diabetes mellitus.
  • Administered AVE7688, a vasopeptidase inhibitor, orally via chow at 45 mg/kg/day for six weeks.

Related Experiment Videos

  • Assessed endothelial function by measuring acetylcholine-mediated relaxation in isolated mesenteric artery rings.

    • Main Results:

    • Demonstrated the presence of endothelial dysfunction in ZDF rats.
    • Chronic administration of AVE7688 (45 mg/kg/day) for six weeks normalized acetylcholine-mediated relaxation in mesenteric artery rings.
    • This normalization indicates a significant improvement in vascular endothelial function.

    Conclusions:

    • The Zucker diabetic fatty rat exhibits endothelial dysfunction, validating its use as a model for T2DM vascular complications.
    • Chronic vasopeptidase inhibition with AVE7688 effectively reversed endothelial dysfunction in this model.
    • Vasopeptidase inhibition represents a potential therapeutic strategy to prevent vascular complications associated with type 2 diabetes mellitus.