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Angiotensin II type‐1 receptor antagonism attenuates the hypercholesterolemia‐induced vascular dysfunction in mouse aorta
Author(s) -
Kurtel Hizir,
Granger D. Neil
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.774.1
Subject(s) - losartan , angiotensin ii receptor type 1 , angiotensin ii , medicine , endocrinology , vasodilation , sodium nitroprusside , phenylephrine , aorta , endothelial dysfunction , endothelium , vasoconstriction , angiotensin ii receptor antagonist , antagonist , nitric oxide , receptor , blood pressure
Objective‐ Hypercholesterolemia induces a prothrombogenic and proinflammatory state that can be effectively reduced by the angiotensin II type 1 (AT1‐R) receptor antagonist losartan. The objective of this study was to determine the role for the AT1‐R in mediating the impaired endothelium‐dependent vasodilation (EDV) normally observed in the aorta of hypercholesterolemic mice. Methods and Results‐Vascular function was assessed in aortic rings by monitoring endothelium‐independent contraction to phenylephrine, endothelium‐independent dilation to sodium nitroprusside, and endothelium‐dependent dilation to acetylcholine (ACh). C57B1/6 mice were placed on a normal (ND) or high‐cholesterol (HCD) diet for 2 weeks. Separate groups of mice were treated with the AT1‐R antagonist losartan (25 mg/kg per day) in drinking water for 7 days. Serum cholesterol concentration in mice placed on the HCD was significantly higher than the mice placed on ND. EDV but not endothelium‐independent vasodilatation or constriction was significantly attenuated in aortic rings from HCD mice compared to their normocholesterolemic counterparts. The impairment in EDV to ACh observed after HCD was significantly attenuated by administration of losartan. Conclusions‐These data indicate that AT1‐R engagement contributes to the impaired EDV elicited by hypercholoesterolemia in mouse aorta. (Supported by HL26441)