Effects of the angiotensin II type 1 receptor antagonist telmisartan on monocyte adhesion and activation in patients with essential hypertension.
Circulating monocytes from hypertensive patients show elevated secretion patterns of pro-inflammatory cytokines, an increased expression of adhesion molecules, and an increased adhesion to vascular endothelial cells. We tested the hypothesis that telmisartan, an angiotensin II type 1 (AT(1)) receptor antagonist, reduces the activation of circulating monocytes from hypertensive patients and diminishes the monocyte-endothelial cell adhesion. Monocytes of 20 hypertensive patients and 20 normotensive controls were isolated by density gradient centrifugation and Dynabeads, and the monocyte adhesion to human aortic endothelial cell monolayers was measured by adhesion assays. To characterize monocyte activation we assessed the expression of activity-related cell surface markers that are also involved in monocyte adhesion to endothelial cells, such as CD11a/b and CD54, as well as the chemokine receptors CCR1, CCR2 and CCR5 before and after telmisartan therapy using flow cytometry. Spontaneous adhesion of monocytes from hypertensive patients and the adhesion after stimulation with angiotensin II were significantly increased compared with those in normotensive controls (p<0.05). Treatment of hypertensive patients with the AT(1) receptor antagonist telmisartan significantly diminished the adhesion of circulating monocytes to human endothelial cells (p=0.02) despite the increase in the expressions of CD11b, CD54 and CCR5 after telmisartan therapy. Reducing monocyte adhesion may be a novel beneficial effect of the AT(1) receptor antagonist telmisartan helping to prevent vascular alterations in hypertension. The mechanism of action remains to be elucidated, since reduction in monocyte adhesion was not attributable to changes in adhesion molecule expression.
Medical Clinic for Gastroenterology, Infectious Disease and Rheumatology, Charité, Medical Faculty, Humboldt University, Berlin, Germany.
Uta
U
Syrbe
Anja
A
Moebes
Jürgen
J
Scholze
Alexander
A
Swidsinski
Yvonne
Y
Dörffel
D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D018122:B7-1 Antigen / Q000187:drug effects / Q000378:metabolism; D051940:B7-2 Antigen / Q000187:drug effects / Q000378:metabolism; D001562:Benzimidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D001565:Benzoates / Q000494:pharmacology / Q000627:therapeutic use*; D040881:CD11a Antigen / Q000187:drug effects / Q000378:metabolism; D039481:CD11b Antigen / Q000187:drug effects / Q000378:metabolism; D016022:Case-Control Studies; D002448:Cell Adhesion / Q000187:drug effects; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D019707:Receptors, Chemokine / Q000187:drug effects / Q000378:metabolism; D000077333:Telmisartan
D047228:Angiotensin II Type 1 Receptor Blockers; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D001562:Benzimidazoles; D001565:Benzoates; D040881:CD11a Antigen; D039481:CD11b Antigen; D019707:Receptors, Chemokine; D018799:Intercellular Adhesion Molecule-1; D000077333:Telmisartan