RGD Reference Report - Effects of combined olmesartan and pravastatin on glucose intolerance and cardiovascular remodeling in a metabolic-syndrome model. - Rat Genome Database

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

Authors: Mizukawa, M  Ohmori, K  Obayashi, A  Ishihara, Y  Yoshida, J  Noma, T  Yukiiri, K  Kosaka, H  Kohno, M 
Citation: Mizukawa M, etal., Hypertens Res. 2009 Jul;32(7):617-24. Epub 2009 May 22.
RGD ID: 5508692
Pubmed: PMID:19461650   (View Abstract at PubMed)
DOI: DOI:10.1038/hr.2009.63   (Journal Full-text)

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-methylglutaryl-coenzyme 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(-1) per day, pravastatin 30 mg kg(-1) 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Metabolic Syndrome  ISOHmgcr (Rattus norvegicus)5508692; 5508692 RGD 
Metabolic Syndrome  IMP 5508692 RGD 

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
metabolic syndrome X pathway  ISOHmgcr (Rattus norvegicus)5508692; 5508692 RGD 
metabolic syndrome X pathway  IMP 5508692 RGD 
Objects Annotated

Genes (Rattus norvegicus)
Hmgcr  (3-hydroxy-3-methylglutaryl-CoA reductase)

Genes (Mus musculus)
Hmgcr  (3-hydroxy-3-methylglutaryl-Coenzyme A reductase)

Genes (Homo sapiens)
HMGCR  (3-hydroxy-3-methylglutaryl-CoA reductase)


Additional Information