This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 51/5/1306    most recent HYPERTENSIONAHA.108.110932v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Nussberger, J. Articles by Mazzolai, L. PubMed PubMed Citation Articles by Nussberger, J. Articles by Mazzolai, L. Related Collections Animal models of human disease Hypertension - basic studies

(Hypertension. 2008;51:1306.)
© 2008 American Heart Association, Inc.

Original Articles

Renin Inhibition by Aliskiren Prevents Atherosclerosis Progression

Comparison With Irbesartan, Atenolol, and Amlodipine

Jürg Nussberger; Jean-François Aubert; Karima Bouzourene; Maxime Pellegrin; Daniel Hayoz; Lucia Mazzolai

From the Service of Vascular Medicine (J.N., J.-F.A., K.B., M.P., D.H., L.M.), Department of Medicine, Lausanne University Hospital, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; and the Department of Internal Medicine (D.H.), Hôpital Cantonal, Fribourg, Switzerland.

Correspondence to Lucia Mazzolai, Service of Vascular Medicine, CHUV, Av Pierre Decker 5, 1011 Lausanne, Switzerland. E-mail lucia.mazzolai{at}chuv.ch

Hypertension is associated with increased risk of cardiovascular diseases. Antihypertensive treatment, particularly blockade of the renin-angiotensin system, contributes to prevent atherosclerosis-mediated cardiovascular events. Direct comparison of different antihypertensive treatments on atherosclerosis and particularly plaque stabilization is sparse. ApoE^–/– mice with vulnerable (2-kidney, 1-clip renovascular hypertension model) or stable (1-kidney, 1-clip renovascular hypertension model) atherosclerotic plaques were used. Mice were treated with aliskiren (renin inhibitor), irbesartan (angiotensin-receptor blocker), atenolol (β-blocker), or amlodipine (calcium channel blocker). Atherosclerosis characteristics were assessed. Hemodynamic and hormonal parameters were measured. Aliskiren and irbesartan significantly prevented atherosclerosis progression in 2-kidney, 1-clip mice. Indeed, compared with untreated animals, plaques showed thinner fibrous cap (P<0.05); smaller lipid core (P<0.05); decreased media degeneration, layering, and macrophage content (P<0.05); and increased smooth muscle cell content (P<0.05). Interestingly, aliskiren significantly increased the smooth muscle cell compared with irbesartan. Despite similar blood pressure lowering, only partial plaque stabilization was attained by atenolol and amlodipine. Amlodipine increased plaque smooth muscle cell content (P<0.05), whereas atenolol decreased plaque inflammation (P<0.05). This divergent effect was also observed in 1-kidney, 1-clip mice. Normalizing blood pressure by irbesartan increased the plasma renin concentration (5932±1512 ng/mL per hour) more than normalizing it by aliskiren (16085±5628 ng/mL per hour). Specific renin-angiotensin system blockade prevents atherosclerosis progression. First, evidence is provided that direct renin inhibition mediates atherosclerotic plaque stabilization. In contrast, β-blocker and calcium channel blocker treatment only partially stabilize plaques differently influencing atherogenesis. Angiotensin II decisively mediates plaque vulnerability. The plasma renin concentration measurement by an indirect method did not confirm the excessive increase of plasma renin concentration reported in the literature during aliskiren compared with irbesartan or amlodipine treatment.

Key Words: hypertension • renin • atherosclerosis • angiotensin • vulnerable plaque