Angiotensin-(1-7) is associated with beneficial effects in
cardiovascular diseases. In this study, we determined the effect of
AVE0991, a nonpeptide
angiotensin-(1-7) receptor agonist, on cardiac function in an animal model of
diabetes mellitus type I. Diabetes was induced in Sprague-Dawley rats by a single injection of
streptozotocin (70 mg/kg). Diabetic and non-diabetic animals were fed with
AVE0991 (20 mg/kg per day) or control chow. Normoglycemic control chow- or AVE0991-fed rats served as controls (n=10/group). After five weeks, metabolic cage experiments were performed to assess metabolic parameters. Six weeks after induction of diabetes, cardiac function was monitored using a Millar-tip
catheter system.
AVE0991 had no effect on any of the investigated hemodynamic parameters under normoglycemic conditions.
Hyperglycemia was comparable in diabetic animals with or without
AVE0991 treatment. Diabetic control rats suffered from severe systolic dysfunction, indicated by a significant decrease in heart rate, left ventricular systolic pressure, systolic blood pressure and an impairment of left ventricular contractility. Administration of
AVE0991 clearly rescued cardiac function under diabetic conditions as indicated by a normalisation of blood pressure and contractility parameters. Our data demonstrates a dominant beneficial impact of
AVE0991 on the diabetic heart, implying a cardioprotective role for
angiotensin-(1-7) under hyperglycemic conditions and thus pointing to new therapeutic strategies using
angiotensin-(1-7) agonists to treat cardiovascular complications in
diabetes mellitus.