Mechanisms of cardiovascular changes in an experimental model of syndrome X and pharmacological intervention on the renin-angiotensin-system.
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.
Miatello
Roberto
R
Department of Pathology, School of Medicine, National University of Cuyo, Mendoza, Argentina. rmiatell@fcm.uncu.edu.ar
Cruzado
Montserrat
M
Risler
Norma
N
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002320:Cardiovascular Physiological Phenomena; D003331:Coronary Vessels / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D005632:Fructose / Q000378:metabolism; D006321:Heart / Q000503:physiopathology; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D023421:Models, Animal; D008955:Models, Cardiovascular; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D005632:Fructose