Abstract 1761: Synergistic Impacts of Pravastatin and Olmesartan on Glucose Tolerance Leading to Enhanced Amelioration of Cardiovascular Redox State and Remodeling in a Metabolic Syndrome Model
Purposes: Since angiotensin receptor blockers and statins are frequently combined in treating patients with metabolic syndrome, we sought to rationalize the combination therapy by evaluating the impacts on glucose tolerance and its cardiovascular consequences in a model of this syndrome.
Methods and Results: We treated the Otsuka Long-Evans Tokushima fatty rats, a model of progressive insulin resistance, with pravastatin (30 mg/kg/day), olmesartan (3 mg/kg/day) or their combination from 5 weeks of age until they were evaluated at 30 weeks of age (each n = 12). Lipid-lowering effect of pravastatin and antihypertensive effect of olmesartan were significantly augmented by co-administration. The area under the glucose curve during the OGTT (A) was significantly suppressed only by combination therapy. Upregulation of adiponectin mRNA expression in visceral adipose tissue seemed to be a mechanism for this (B). As for cardiovascular effects, cardiac dihydrofolate reductase, an eNOS coupler, was increased by the combination (C) despite the similar total eNOS content among the groups, implying eNOS re-coupling by the combined therapy, which most significantly limited aortic superoxide production with DHE stain (D). As a result, perivascular fibrosis of intramyocardial coronary arteries was most significantly limited by the combined therapy (E).
Conclusion: Olmesartan and pravastatin synergistically ameliorated glucose tolerance in a model of metabolic syndrome, partially through upregulation of adiponectin production. Glucose tolerance thus improved further enhanced known favorable effects of each agent on cardiovascular redox state and histological remodeling.