title: High glucose levels abolish antiatherosclerotic benefits of ACE inhibition in alloxan-induced diabetes in rabbits.
abstract: Renin-angiotensin system activation is recognized to play an important role in atherosclerosis. This study aimed to verify the antiatherosclerotic effects of ACE inhibition on an experimental model of diabetes and hypercholesterolemia. Diabetes was induced in New Zealand male rabbits with a single dose of alloxan (100 mg/kg, i.v.), and, according to plasma glucose levels obtained after 1 week, the animals were divided into 2 groups (> or =250 mg/dL or <250 mg/dL). Each group was randomly assigned to receive or not quinapril (30 mg/d) added to a 0.5% cholesterol-enriched diet. Animals with high glucose levels at 1 week and that remained high after 12 weeks presented higher triglyceride levels (P < 0.02 versus basal). Those initially hyperglycemic but presenting <250 mg/dL glucose at the end of study formed an additional group. Plasma ACE activity was lower in quinapril-treated animals (P < 0.01 versus untreated groups). However, aorta intima/media ratio and intima area were lower only in the subgroups of quinapril-treated animals with low glucose levels (P < 0.05). Our results support the hypothesis that high plasma glucose may abolish the antiatherosclerotic effect of ACE inhibitors.
authors.affiliation: Department of Pathology, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Pomaro
authors.forename: Silvia S M
authors.initials: SS
authors.lastname: Ihara
authors.forename: Leonor E S A
authors.initials: LE
authors.lastname: Pinto
authors.forename: Ivete
authors.initials: I
authors.lastname: Ueda
authors.forename: Dulce E
authors.initials: DE
authors.lastname: Casarini
authors.forename: Fabiana
authors.initials: F
authors.lastname: Ebihara
authors.forename: Andreza O
authors.initials: AO
authors.lastname: Santos
authors.forename: Maria C O
authors.initials: MC
authors.lastname: Izar
authors.forename: Francisco A H
authors.initials: FA
authors.lastname: Fonseca
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001161:Arteriosclerosis / Q000097:blood / Q000188:drug therapy*; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy*; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy; D008297:Male; D000077583:Quinapril; D011817:Rabbits; D044005:Tetrahydroisoquinolines / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D001786:Blood Glucose; D044005:Tetrahydroisoquinolines; D000077583:Quinapril