Influence of angiotensin II on circulating adhesion molecules and blood leukocyte count in vivo.
The mechanism of the beneficial effect of angiotensin converting enzyme inhibitors in patients with myocardial infarction is not clear. Recent in vitro data indicate that angiotensin II (AII) stimulates the expression of adhesion molecules and thus activates leukocyte endothelial interactions. In eight healthy volunteers we investigated the influence of exogenous AII on circulating adhesion molecules and on the blood leukocyte count. A systemically effective and a systemically ineffective dose of AII were administered intravenously over 4 h in a single blind crossover design. Examination of the time course of circulating intercellular and vascular adhesion molecules and E-selectin (cICAM-1, cVCAM-1, cE-selectin-1) in response to the AII infusion revealed increases of up to 11% (especially in cVCAM-1 levels) at single time points, but no significant sustained elevation or trend that can be interpreted as a drug-induced effect. The systemically effective dose, which induced an increase in mean arterial blood pressure from 80 to 108 mmHg (1 mmHg = 133.3 Pa), resulted in a significant increase in blood leukocytes, from 4.8 +/- 0.3 to 5.5 +/- 0.3 g/L (p < 0.05); the systemically ineffective AII dose did not alter blood leukocyte count significantly. Although we did not find an influence of AII on circulating adhesion molecules in vivo, we observed an increase in the blood leukocyte count; thus it may be intriguing to assess whether renin-angiotensin system modulating drugs might exert their favorable effect in ischemic diseases at least in part via an influence on leukocytes.
Krejcy
K
K
Department of Clinical Pharmacology, University of Vienna, Austria.
Eichler
H G
HG
Jilma
B
B
Kapiotis
S
S
Wolzt
M
M
Zanaschka
G
G
Gasic
S
S
Schütz
W
W
Wagner
O
O
D000328:Adult; D000804:Angiotensin II / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects*; D002452:Cell Count / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects; D007962:Leukocytes / Q000187:drug effects*; D008297:Male; D013997:Time Factors; D019010:Vascular Cell Adhesion Molecule-1 / Q000187:drug effects
D019010:Vascular Cell Adhesion Molecule-1; D000804:Angiotensin II; D018799:Intercellular Adhesion Molecule-1