Effects of enalapril and losartan on circulating adhesion molecules and monocyte chemotactic protein-1.
At least four independent studies in different clinical settings showed that angiotensin-converting enzyme inhibitors (ACE-Is) such as enalapril effectively decrease plasma levels of circulating adhesion molecules (cAMs). To examine whether this effect may be mediated by the decreased action of angiotensin, we compared the effects of enalapril with the direct angiotensin-II antagonist, losartan, on plasma levels of cAMs, and monocyte chemotactic protein-1 (MCP-1). In a randomized trial, we recruited 32 untreated patients (19 male, aged 59+/-13 years) with hypertension, who received either enalapril (mean dose 17 mg/day) or losartan (mean dose 77 mg/day) at equipotent doses. Enalapril decreased plasma levels of all cAMs after 8 weeks of treatment: cE-selectin levels decreased by 13% (P=0.007), intercellular adhesion molecule-1 (cICAM-1) by 15% (P=0.002) and vascular cell adhesion molecule-1 (cVCAM-1) by 19% (P=0.003). Similarly, enalapril decreased plasma levels of MCP-1 by 13% (P<0.001). Losartan did not significantly change cAM or MCP-1 plasma concentrations after 8 weeks of treatment: cE-selectin levels decreased by 3%, cICAM-1 by 5%, cVCAM-1 by 8%, whereas MCP-1 increased by 2% (all P=NS; not significant). The enalapril effect on percentage changes of cVCAM-1 was significantly different from losartan (P=0.0429). Eight weeks of antihypertensive treatment with enalapril but not losartan, significantly decreased plasma levels of cAMs and MCP-1 in hypertensive patients. The beneficial effects of ACE-Is on cAMs may have implications for atherogenesis and the reduction of cardiovascular events, which cannot be fully explained by their antihypertensive effects alone.
Jilma
B
B
Department of Clinical Pharmacology - TARGET, University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria. Bernd.Jilma@univie.ac.at
Li-Saw-Hee
F L
FL
Wagner
O F
OF
Beevers
D G
DG
Lip
G Y H
GY
D000368:Aged; D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D015815:Cell Adhesion Molecules / Q000097:blood*; D018932:Chemokine CCL2 / Q000097:blood*; D004311:Double-Blind Method; D019040:E-Selectin / Q000097:blood; D004656:Enalapril / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
D000806:Angiotensin-Converting Enzyme Inhibitors; D015815:Cell Adhesion Molecules; D018932:Chemokine CCL2; D019040:E-Selectin; D004791:Enzyme Inhibitors; D019010:Vascular Cell Adhesion Molecule-1; D000804:Angiotensin II; D018799:Intercellular Adhesion Molecule-1; D004656:Enalapril; D019808:Losartan