Effects of pravastatin on progression of glucose intolerance and cardiovascular remodeling in a type II diabetes model

Yu, Yang; Ohmori, Koji; Chen, Yan; Sato, Chubun; Kiyomoto, Hideyasu; Shinomiya, Kaori; Takeuchi, Hiroto; Mizushige, Katsufumi; Kohno, Masakazu

doi:10.1016/j.jacc.2004.04.050

Cited by 69 publications

(71 citation statements)

References 42 publications

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“…Male Otsuka Long-Evans Tokushima Fatty (OLETF) rats fed with normal chow were treated with either OLM (3 mg kg À1 per day), PRA (30 mg kg À1 per day: 30% of the full dose tested in our earlier studies 10,11 ), or their combination (OLM+PRA) (n¼12 for each) from 5 weeks of age. Agents were suspended in drinking water at concentrations adjusted according to the amount of water consumed during the preceding 2 days, so that the total scheduled doses were administered.…”

Section: Animals and Experimental Protocolmentioning

confidence: 99%

“…At 30 weeks of age, blood was sampled from the right jugular vein after an overnight fast and the oral glucose (2 g kg À1 body weight) tolerance test (OGTT) was applied as described elsewhere. 10,11,17 Then, all the rats were killed after administering deep anesthesia with i.p. sodium pentobarbital (50 mg kg À1 ), and the heart, aorta and epididymal WAT were excised.…”

Section: Animals and Experimental Protocolmentioning

confidence: 99%

“…Insulin resistance was evaluated based on the product of fasting glucose and insulin concentrations. 10,11 Tissue processing Short-axis sections (3-mm thick) of the left ventricle at the mid-ventricular level and aorta samples were fixed with formalin or frozen in an optimal cutting temperature (OCT) compound and stored at À80 1C until histological assessment. The remaining tissue samples and WAT were immediately frozen in liquid nitrogen and stored at À80 1C before total RNA and/or protein extraction.…”

Section: Biochemical Analyses Of Blood Samplesmentioning

confidence: 99%

“…We determined the wall-to-lumen ratio (medial thickness compared with luminal diameter) and the ratio of the area of perivascular fibrosis to the vascular cross-sectional area in 5-10 cross-sections of arteries between 30 and 200 mm in diameter, as described earlier, 10,11,19 which were reported as percentage of the values for the normal LETO rats.…”

Section: Histochemical and Histological Analysismentioning

confidence: 99%

“…[6][7][8] We and others have shown that PRA upregulates adiponectin messenger RNA expression in adipose tissue 8 and in cultured adipocytes, 9 and prevents the development of DM in animal models. [9][10][11] Clinical studies have also shown that PRA treatment increases plasma adiponectin in patients with hypercholesterolemia and is associated with improved glucose metabolism. 8,9 As dyslipidemia often accompanies hypertension, such individuals are frequently treated with both reninangiotensin system inhibitors and statins.…”

Section: Introductionmentioning

confidence: 99%

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Effects of combined olmesartan and pravastatin on glucose intolerance and cardiovascular remodeling in a metabolic-syndrome model

et al. 2009

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Hypertension and dyslipidemia frequently coexist in patients with progressive insulin resistance and thus constitute metabolic syndrome. We sought to determine the merits of combining an angiotensin II receptor blocker and a 3-hydroxy-3-methylglutarylcoenzyme A reductase inhibitor in treating this pathological condition. Five-week-old Otsuka Long-Evans Tokushima Fatty rats, a model of metabolic syndrome, were untreated or treated with olmesartan 3 mg kg À1 per day, pravastatin 30 mg kg À1 per day or their combination for 25 weeks. Long-Evans Tokushima Otsuka rats served as normal controls. The antihypertensive effect of olmesartan and the lipid-lowering properties of pravastatin were both augmented by the combination. The oral glucose tolerance test revealed that only the combined treatment significantly reduced the area under the time-glucose curve, which was accompanied by augmented adiponectin messenger RNA expression in epididymal adipose tissue. Although the total cardiac endothelial nitric oxide synthetase (eNOS) content did not significantly differ among the groups, the combined treatment significantly increased the content of dihydrofolate reductase, a key eNOS coupler. Dihydroethidium staining of the aorta showed that the combination most significantly attenuated superoxide production. Moreover, Azan-Mallory staining revealed that the combination most significantly limited the perivascular fibrosis and wall thickening of intramyocardial coronary arteries. In conclusion, the combination of olmesartan and pravastatin augmented adiponectin expression in white adipose tissue and improved glucose tolerance in a rat model of metabolic syndrome, which was associated with more significant ameliorations of cardiovascular redox state and remodeling than those by treatments with either agent alone.

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Section: Animals and Experimental Protocolmentioning

confidence: 99%

Section: Animals and Experimental Protocolmentioning

confidence: 99%

Section: Biochemical Analyses Of Blood Samplesmentioning

confidence: 99%

Section: Histochemical and Histological Analysismentioning

confidence: 99%