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.

Impaired glucose tolerance plus hyperlipidaemia induced by diet promotes retina microaneurysms in New Zealand rabbits

“…The diet was very well tolerated, and all the animals survived the study protocol and did not show infectious disease. In the alloxan model, besides producing type 1 diabetes, there is a high mortality rate because of acute pancreatic insufficiency (Srinivasan and Ramarao, 2007; Pomaro et al. 2005).…”

Altered glucose metabolism and hypoxic response in alloxan-induced diabetic atherosclerosis in rabbits

“…Experiments proceeded under aseptic conditions and general anaesthesia induced via subcutaneous administration of medetomidine (0.16mg/kg) and butorphanol tartrate (0.4mg/kg) and intravenous infusion of midazolam (0.6 mg/kg). Diabetic rabbits were generated from Japanese white rabbits initially weighing 2.5–3.5 kg using a single dose of alloxan [13]. Atherosclerotic lesions were produced by feeding the rabbits with a high-cholesterol diet and denuding the endothelium of the femoral arteries in diabetic and non-diabetic rabbits.…”

Animal Models of Calcific Aortic Valve Disease

“…For example, rabbit comorbidity models include diabetes [153], hypertension [154], metabolic syndrome [155, 156], and high serum calcium [80, 82], along with hypercholesterolemia. Porcine models have also combined diabetes [106, 108, 110–112] or hypertension [157] with diet-induced hypercholesterolemia.…”