Chronic vasopeptidase inhibition normalizes diabetic endothelial dysfunction.
Type 2 diabetes mellitus is a major cause of vascular morbidity but animal models for this disease have not been adequately characterized. We demonstrate that endothelial dysfunction is present in the Zucker diabetic fatty (ZDF) rat. Vasopeptidase inhibition with AVE7688 (7-[[(2S)-2-(acetylthio)-1-oxo-3-methylpropyl]amino]-1,2,3,4,6,7,8,12b-octahydro-6-oxo-(4S,7S,12bR)-pyrido[2,1-a][2]benzazepine-4-carboxic acid), 45 mg/kg/day in chow for 6 weeks, normalized acetylcholine mediated relaxation of mesenteric artery rings. Thus, chronic vasopeptidase inhibition may prevent vascular complications related to type 2 diabetes mellitus.
Schäfer
Stefan
S
Disease Group Cardiovascular Diseases, Building H 821, Aventis Pharma Deutschland GmbH, D-65926 Frankfurt am Main, Germany. stefan.schaefer@aventis.com
Steioff
Kerstin
K
Linz
Wolfgang
W
Bleich
Markus
M
Busch
Andreas E
AE
Löhn
Matthias
M
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000201:enzymology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology*; D006575:Heterocyclic Compounds, 3-Ring / Q000008:administration & dosage; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000201:enzymology; D011480:Protease Inhibitors / Q000008:administration & dosage*; D051381:Rats; D011924:Rats, Zucker; D012084:Renin-Angiotensin System / Q000187:drug effects
C479877:AVE 7688; D006575:Heterocyclic Compounds, 3-Ring; D011480:Protease Inhibitors