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January 1, 2012The Tohoku Journal of Experimental MedicineOpen Access

Anti-Atherogenic Effects of the Combination Therapy with Olmesartan and Azelnidipine in Diabetic Apolipoprotein E-Deficient Mice

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Key result

Combination therapy with olmesartan and azelnidipine significantly suppressed aortic atherosclerosis and reactive oxygen species production in diabetic ApoE-/- mice independent of blood pressure lowering.

Why the study?

Does combination therapy with olmesartan and azelnidipine prevent atherosclerosis in diabetic ApoE-/- mice?

Population

Male control and streptozocin-induced diabetic Apolipoprotein E-deficient (ApoE-/-) mice

Comparison

Combination therapy with olmesartan and… vs Vehicle, olmesartan alone, azelnidipine alone…

Design

Preclinical

Follow-up

5 weeks

Authors

KNKazuki NodaHiroshima UniversityMHMaki HosoyaTohoku UniversitySNSota NakajimaSendai City Hospital

Discussion

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Implication

Hypothesis-generating for anti-atherosclerotic effects of olmesartan-azelnidipine in diabetes; human trials required before any clinical consideration.

Structured PICO

Does combination therapy with olmesartan and azelnidipine prevent atherosclerosis in diabetic ApoE-/- mice?

P
Population
36 male 8-week-old streptozocin-induced diabetic ApoE-/- mice and controls treated for 5 weeks to evaluate anti-atherogenic effects.
I
Intervention
Combination therapy with olmesartan (30 mg/kg/day) and azelnidipine (10 mg/kg/day) orally for 5 weeks
C
Comparator
Vehicle (Untreated), olmesartan alone, azelnidipine alone, or hydralazine (5 mg/kg/day) as an antihypertensive control
O
Outcome
Atherosclerosis area in the thoracic aorta, perivascular fibrosis and medial thickness of the coronary arteriessurrogate

Main Result

p-value: p=<0.05

Combination therapy with olmesartan and azelnidipine exerts anti-atherogenic effects in diabetic mice through suppression of oxidative stress and activation of eNOS, independent of blood pressure lowering.

Limitations

  • The diabetic ApoE-/- mouse model is an extreme animal model of atherosclerosis.
  • Relatively higher doses of OLM and AZL were used as compared with the clinical setting.
  • Many other factors related to oxidative stress remain to be examined.
  • It remains to be examined whether the beneficial effects of the combination therapy ameliorates long-term prognosis.
  • Insulin secretion or insulin sensitivity were not examined in this type 1 diabetes model.

Cite This Study

Noda et al. (2012) studied Atherosclerosis in diabetes (n=36). Olmesartan and Azelnidipine combination vs. Vehicle, OLM alone, AZL alone, or Hydralazine was evaluated on Aortic atherosclerosis area (p=<0.05). Combination therapy with olmesartan and azelnidipine significantly suppressed aortic atherosclerosis and reactive oxygen species production in diabetic ApoE-/- mice independent of blood pressure lowering.

synapsesocial.com/papers/6a7c99aa1c66e457e78ce40bhttps://doi.org/10.1620/tjem.228.305
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