Angiotensin II type 1 receptor antagonism improves hypercholesterolemia-associated endothelial dysfunction.

Abstract

OBJECTIVE:

Hypercholesterolemia-induced angiotensin II type 1 (AT1) receptor overexpression is thought to be a key event in the development of endothelial dysfunction.

METHODS AND RESULTS:

The effect of a 6-week treatment with the AT1 receptor antagonist candesartan (16 mg/d) on endothelial function and serum inflammation markers was compared with the effect of treatment with placebo or the calcium channel antagonist felodipine (5 mg/d) in 47 hypercholesterolemic patients (low density lipoprotein cholesterol >160 mg/dL). Endothelial function was assessed by measurement of forearm blood flow (FBF) by venous occlusion plethysmography. FBF during reactive hyperemia was significantly improved by candesartan, whereas felodipine and placebo exerted no effect. Nitroglycerin-induced vasorelaxation and basal FBF were not altered significantly. Blood pressure and cholesterol levels were not affected significantly by any drug. Serum concentrations of 8-isoprostane, monocyte chemoattractant protein-1, and soluble intercellular adhesion molecule-1 were significantly reduced by candesartan treatment but not by placebo or felodipine (ELISA assays). Levels of high-sensitivity C-reactive protein and tumor necrosis factor-alpha were not altered significantly by any treatment.

CONCLUSIONS:

These data suggest that AT1 receptor antagonism improves endothelial function during hypercholesterolemia and that this applies not only to endothelium-dependent vasodilatation but also to oxidative stress and events involved in monocyte attraction and adhesion. AT1 receptor blockade may potentially represent a novel approach for the prevention of vascular dysfunction associated with hypercholesterolemia that is independent of lipid-lowering and blood pressure-lowering interventions.

• Authors: Sven Wassmann, Stefan Hilgers, Ulrich Laufs, Michael Böhm, Georg Nickenig
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 22 Issue 7 Pg. 1208-12 (Jul 01 2002) ISSN: 1524-4636 [Electronic] United States
• PMID: 12117739 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin Receptor Antagonists
• Antihypertensive Agents
• Benzimidazoles
• Biomarkers
• Biphenyl Compounds
• Calcium Channel Blockers
• Cholesterol, LDL
• Receptor, Angiotensin, Type 1
• Receptors, Angiotensin
• Tetrazoles
• Angiotensin II
• Felodipine
• candesartan

Topics

• Angiotensin II (antagonists & inhibitors)
• Angiotensin Receptor Antagonists
• Antihypertensive Agents (pharmacology, therapeutic use)
• Benzimidazoles (pharmacology, therapeutic use)
• Biomarkers (blood)
• Biphenyl Compounds
• Blood Pressure (drug effects)
• Calcium Channel Blockers (pharmacology, therapeutic use)
• Cholesterol, LDL (blood)
• Double-Blind Method
• Endothelium, Vascular (drug effects, metabolism, physiopathology)
• Felodipine (pharmacology, therapeutic use)
• Female
• Forearm (blood supply)
• Humans
• Hypercholesterolemia (blood, drug therapy, metabolism, physiopathology)
• Inflammation (blood, drug therapy)
• Male
• Middle Aged
• Prospective Studies
• Receptor, Angiotensin, Type 1
• Receptors, Angiotensin (physiology)
• Regional Blood Flow (drug effects)
• Tetrazoles (pharmacology, therapeutic use)