Angiotensin receptor blockade decreases markers of vascular inflammation.
A protective role against atherosclerosis can be attributed to angiotensin converting enzyme inhibitors (ACE-I), since they have been shown to reduce mortality in patients at cardiovascular risk. Since plasma levels of adhesion molecules are considered surrogate markers of endothelial cell activation and atherogenesis, we compared the levels of adhesion molecules after treatment with the ACE-I enalapril or the direct angiotensin- receptor antagonist losartan or placebo. In a randomized, controlled trial, 21 hypercholesterolemic volunteers received 50 mg/d losartan or 20 mg/d enalapril or placebo for twelve weeks. Plasma levels of circulating intercellular adhesion molecule-1 (cICAM-1), vascular adhesion molecule-1 (cVCAM-1), and E-selectin (cE-SEL) were measured by ELISA. Surface expression of ICAM-1 on circulating leukocytes was determined by flow cytometry. Enalapril and losartan but not placebo induced a small but stable decrease of cICAM-1 and cVCAM-1, while cE-SEL and leukocyte expression of ICAM-1 remained unchanged. The lowering of plasma adhesion molecules may indicate an antiatherogenic effect of angiotensin II blockade in hypercholesterolemia. While such preventive effect will have to be proven in clinical trials, our results do not support a preference for either enalapril or losartan with regard to their possible vasoprotective role.
Department of Clinical Pharmacology, Vienna University, Vienna, Austria. monika.graninger@univie.ac.at
Monika
M
Graninger
Rosemarie
R
Reiter
Christa
C
Drucker
Erich
E
Minar
Bernd
B
Jilma
D057911:Angiotensin Receptor Antagonists; D001794:Blood Pressure / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D004311:Double-Blind Method; D019040:E-Selectin / Q000097:blood; D004656:Enalapril / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D006937:Hypercholesterolemia / Q000175:diagnosis / Q000188:drug therapy; D007249:Inflammation / Q000175:diagnosis / Q000235:genetics / Q000517:prevention & control*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood / Q000187:drug effects; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology; D019808:Losartan / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011945:Receptors, Angiotensin / Q000627:therapeutic use*; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood / Q000187:drug effects; D014652:Vascular Diseases / Q000175:diagnosis / Q000235:genetics / Q000517:prevention & control*
D057911:Angiotensin Receptor Antagonists; D019040:E-Selectin; D011945:Receptors, Angiotensin; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D004656:Enalapril; D002784:Cholesterol; D019808:Losartan