The angiotensin-(1-7) receptor agonist AVE0991 is cardioprotective in diabetic rats.
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.
Department of Cardiology, Charité, Campus Benjamin Franklin, Berlin, Germany.
Linda
L
Ebermann
Frank
F
Spillmann
Melanie
M
Sidiropoulos
Felicitas
F
Escher
Silvia
S
Heringer-Walther
Heinz-Peter
HP
Schultheiss
Carsten
C
Tschöpe
Thomas
T
Walther
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000819:agonists*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000819:agonists*; D013311:Streptozocin; D016277:Ventricular Function, Left / Q000187:drug effects
C469726:AVE 0991; D007093:Imidazoles; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D009569:Nitric Oxide; D013311:Streptozocin