Mechanisms of Cardiovascular Changes in an Experimental Model of Syndrome X and Pharmacological Intervention on the Renin-Angiotensin- System

Abstract

Various cardiovascular risk factors and disease states similar to those present in type 2 diabetic patients also seem to be present in non-diabetic individuals. This cluster of risk factors has been called syndrome X, also known as metabolic cardiovascular syndrome or insulin resistance syndrome. Vascular wall components changes, including endothelial dysfunction and vascular smooth muscle cell (VSMC) migration and proliferation, could be involved in the cardiovascular alterations associated with this state. Fructose fed rats (FFR) provide a model of dietary-induced insulin resistance, which has been used to assess the pathophysiological mechanisms of the metabolic and cardiovascular changes associated to the syndrome X. FFR have hyperinsulinemia, insulin resistance (altered glucose tolerance test) and hypertriglyceridemia; they also develop moderate hypertension and cardiac hypertrophy. This has been confirmed in male rats of different strains, such as Wistar and Sprague-Dawley, chronically fed with a 60% fructose-chow or 10% fructose in the drinking water. At different levels of the cardiovascular system, FFR exhibit changes in the nitric oxide generation system and in primary cultured proliferation of VSMC from conduit and resistance arteries. These abnormalities were normalized by long-term treatment with pharmacological agents acting on the renin-angiotensin system (RAS), such as angiotensin converting-enzyme inhibitors or angiotensin-AT(1) receptor antagonists, that also lowered blood pressure to control levels and reversed cardiac hypertrophy. Evidence suggests an important role for the RAS in the pathogenic mechanisms involved in this model of syndrome X. Furthermore, beneficial pharmacological intervention seems to be mediated by AT(2) receptors and kinins.

Effect of Red Wine on Adipocytokine Expression and Vascular Alterations in Fructose-Fed Rats

“…Previous studies have shown the key role of NAD(P)H-oxidase in the vascular oxidative stress, vascular smooth muscle cells proliferation, endothelial dysfunction, and development of hypertension. 4,5,20 Moreover, Nyby et al 33 have shown that increased ROS production by NAD(P)H-oxidase was associated with vascular inflammation assessed through VCAM-1 mRNA expression and vascular dysfunction in FFR. On the other hand, Sarr et al 34 showed that RW polyphenols prevented endothelial dysfunction, vascular ROS production, and NAD(P)H-oxidase expression in rats infused with angiotensin II-induced hypertension.…”

“…Nox4 subunit expression is strongly correlated with an increase of NAD(P)H-oxidase activity. 6 Our group previously reported an enhanced NAD(P)H-oxidase aorta activity 5 and higher plasma lipid peroxidation 7 in FFR implying that this model of MS is characterized by oxidative stress.…”

“…1 Fructose intake has increased dramatically in the past 20 years contributing to the growing worldwide prevalence of MS, obesity, and diabetes. 2,3 Fructose-fed rats (FFRs) provide a model of dietary-induced insulin resistance, which has been used to assess the pathophysiological mechanisms involved in the metabolic and cardiovascular changes associated with MS. 4,5 Oxidative stress has been implicated in the pathogenesis of many cardiovascular diseases. The major sources of reactive oxygen species (ROS) in vascular tissue are membraneassociated NAD(P)H-oxidases, also known as Nox enzymes.…”

Cardiac and metabolic changes in long-term high fructose-fat fed rats with severe obesity and extensive intramyocardial lipid accumulation

“…Both high-fructose-and high-sucrose-fed rats show increased fasting glucose and triglyceride levels, and high-fructose-fed rats develop glucose intolerance and insulin resistance (5,6,17,18,25). Furthermore, several studies have found that a diet rich in fructose or sucrose induces hypertension in rats (11,26,33,40,44,45), whereas a few studies have reported that fructose does not affect blood pressure (BP) (1,41).…”

Organosulfur compounds and cardiovascular disease

“…Metabolic syndrome, characterized by hypertension, hyperglucemia, hyperlipidemia, is another well-known risk factor for cardiovascular disease (Isomaa et al, 2001;Miatello et al, 2004). Oxidative stress and vascular remodeling is also reported in this model Renna et al, 2009).…”