Are Zucker obese rats a useful model for cardiovascular complications in metabolic syndrome? Physical, biochemical and oxidative stress considerations

Abstract

We wondered if Zucker obese (ZO) rats would be a good experimental model to evaluate cardiovascular complications of metabolic syndrome (MS). ZO rats were compared with both their littermate controls, Zucker lean (ZL) rats and to Wistar rats (reference strain). We designed this work:(i) to measure certain physical and biochemical characteristics of MS; (ii) to evaluate coronary and cardiac function in isolated conditions and after ischemia; and (iii) to study plasma and heart tissue oxidative stress markers. In vivo, ZO rats had higher levels of plasma glucose, cholesterol and triglycerides than their ZL littermates, but there was no difference between the groups for systolic arterial blood pressure and heart rate. In vitro, coronary endothelial function was notably impaired in ZO and ZL rats. After global ischemia, the worse ventricular recovery in ZO and ZL rats was associated with arrhythmias during reperfusion. We detected similar levels of plasma ascorbyle free radical, oxygen radical absorbance capacity and vitamin C concentrations in the three groups. Dihydroethidium staining showed higher superoxide production in the coronary vessels of ZO rats than in ZL and Wistar rats. Our results show that ZO might only correspond to early‐stage cardiovascular complications associated with MS.

Coronary vascular dysfunction promoted by oxidative‐nitrative stress in SHRSP.Z‐Leprfa/IzmDmcr rats with metabolic syndrome

“…In contrast to our data in the SHRSP fatty rats, it was reported that NO mediated dilation in coronary arteries was not altered in Zucker obese rats 5,7,9,11 and in Wistar Ottawa Karlsburg W rats, 4 both are models of metabolic syndrome. The absence of NO‐mediated coronary artery dysfunction was also reported in fructose‐loaded insulin‐resistant rats 10 and diabetic db/db mice, 8 which display normal or only slightly increased blood pressure.…”

“…In blood vessels, it has been shown that superoxide anion is produced by NADPH oxidase activation secondary to angiotensin II stimulation 17 . In Zucker obese rats, coronary dysfunction mediated by increased production of reactive oxygen species by vascular NADPH oxidase has been observed in isolated coronary arteries using myography techniques and in perfusion studies of isolated hearts 5,9,11 . In the present study, we found an increased production of not only superoxide, but also 3‐nitrotyrosine, which has been considered to be a footprint for peroxynitrite, in the arteries of SHRSP fatty rats.…”

“…However, these studies were not able to characterize vascular reactivity, oxidative stress specific to vascular tissue, and the mechanisms responsible for producing oxidative and nitrative stress. In the parent strains, SHRSP 16 and Zucker obese 5,9 rats, an increased production of reactive oxygen species by vascular NADPH oxidase activation, which was secondary to angiotensin II type 1 receptor stimulation, 17 has been observed. Therefore, oxidative stress in vascular tissues induced by angiotensin II would appear to be an important first mechanism to investigate in order to explain vascular dysfunction in the SHRSP model of metabolic syndrome.…”

“…The impact of experimental metabolic syndrome on coronary microvascular function has been equivocal. Coronary vasodilator responses have been shown to be unchanged, enhanced 4–7 or impaired 8–11 in Zucker obese rats, Wistar Ottawa Karlsburg W rats, fructose‐loaded insulin‐resistant rats and db/db mice when these models of metabolic syndrome were compared with control animals. Recent studies show that oxidative stress plays an important role in the pathology of metabolic syndrome, 12 so reactive oxygen species might be a factor contributing to the different findings between animal models.…”

Role of NAD(P)H Oxidase in Superoxide Generation and Endothelial Dysfunction in Goto-Kakizaki (GK) Rats as a Model of Nonobese NIDDM

“…The GK rats are a nonobese model of NIDDM that have elevated fasting glucose, impaired response to glucose, and increased HbA1c levels at an early age [9], [10], [11]. Compared to other diabetic animal models, including the Zucker fa/fa and Lepr db mouse, the GK rats are not severely hyperlipidemic or hypercholesterolemic and present as a model of hyperglycemia [7], [12]. Therefore, the objective of this study was to elucidate whether endothelial or smooth muscle dysfunction was evident in the hyperglycemic GK rats and the potential role NADPH oxidase function may have.…”