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(Hypertension. 1998;32:1044-1048.)
© 1998 American Heart Association, Inc.

Scientific Contributions

₁-Adrenergic Plus Angiotensin Receptor Blockade Reduces Atherosclerosis in Apolipoprotein E–Deficient Mice

Konstantinos P. Makaritsis; Haralambos Gavras; Yue Du; Aram V. Chobanian; Peter Brecher

From the Departments of Medicine and Biochemistry, Boston University School of Medicine, Boston, Mass.

Correspondence to Peter Brecher, PhD, Boston University School of Medicine, 715 Albany St, W507, Boston, MA 02118. E-mail pbrecher{at}bu.edu

Abstract—We have used the apolipoprotein E (apoE)–deficient mouse model to determine whether both the angiotensin II type 1 (AT₁) and the ₁-adrenergic receptors influence arteriosclerotic changes in this hyperlipidemic animal model. Mice were treated with antihypertensive drugs beginning at 9 weeks of age, and aortic atherosclerosis was measured after 12 weeks of treatment. Systolic blood pressure in the untreated apoE-deficient mouse averaged 104 mm Hg throughout the treatment period. Prazosin at a dose of 7.5 mg · kg^-1 · d^-1 was ineffective in attenuating atherosclerosis and did not significantly reduce blood pressure. Losartan, at dosages of either 20 or 30 mg · kg^-1 · d^-1, also did not influence atherosclerosis and had only a slight blood pressure–lowering effect. However, combined treatment with both prazosin and losartan markedly reduced atherosclerotic lesion development from an average lesion size per section of 2.6 to 1.5x10⁵ µm² (P<0.001) and significantly reduced blood pressure to 85±5 mm Hg. Treatment with N^G-nitro-L-arginine methyl ester (40 mg · kg^-1 · d^-1) produced significant elevations of blood pressure (127±3.8 mm Hg) but had no effect on the development of atherosclerosis. None of the treatments used affected plasma cholesterol throughout the 12-week period. These studies suggest that the vascular changes associated with atherosclerosis are influenced by a combination of AT₁ and ₁-adrenergic receptor activation.

Key Words: atherosclerosis • blood pressure • losartan • prazosin • mice • hypercholesterolemia

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