Experimental study on preventive effects of statin and ARB for metabolic syndrome : using a new animal model, obese stroke-prone spontaneous hypertensive rats

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SHRSP/IDmcr-fa/fa (SHRSP/fatty) rats are a new animal model that have the potential to develop severe hypertension, obesity, hyperlipidemia, and hyperglycemia, followed by arteriopathy and glomerulopathy in the kidneys. Thus, SHRSP/fatty rats seem to be the most severe animal model of human metabolic syndrome. Using this unique animal model, we investigated how HMG-CoA reductase inhibitor (statin), a well-known drug for hypercholesterolemia, and angiotensin II receptor blocker (ARB), a widely-used anti-hypertensive drug, affected the pathophysiology related to metabolic syndrome. The statin increased the mRNA expression of adiponectin and leptin, decreased the expression of TNF-alpha gene, and increased the secretion of high molecular weight (HMW) adiponectin, without a lipid-lowering effect. ARB increased both total adiponectin and HMW adiponectin, independent of blood pressure lowering. Histologically, the incidence of renal lesions, such as angionecrosis and glomerulosclerosis, was decreased in both treated groups. Except for well-known pharmacological effects of these drugs, the additional medicinal benefit of the statin depended on its anti-inflammatory effect, and that of ARB probably depended on its direct effect on adipocytes. It was considered that the increase of HMW adiponectin was enhanced by both pathways, and this may be a common factor of the protective effects of both drugs on pathophysiological damages in SHRSP/fatty rats.

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