(Hypertension. 1999;34:113-117.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
From the Outpatient Clinics of Internal Medicine (Y.D., C.L., J.S.), and the Department of Rheumatology and Clinical Immunology (B.S., S. Scholze, G.R.B.), Charité University Hospital, Humboldt University, Berlin, and First Medical Department, Christian Albrecht University, Kiel, (S. Schreiber) Germany.
Correspondence to Yvonne Dörffel, MD, Humboldt University, Charité, Medical Faculty, Outpatient Clinics of Internal Medicine, Luisenstrasse 11-13, 10098 Berlin, Germany. E-mail yvonne.doerffel{at}charite.de
AbstractThe purpose of this
study was to investigate the possible involvement of human
peripheral blood monocytes in the pathology of hypertensive
disease. We determined the in vitro secretion patterns of
proinflammatory cytokines obtained from isolated
peripheral monocytes from normal controls and from
hypertensive patients either after in vitro stimulation with
angiotensin II (Ang II) with or without preincubation with
an Ang II type 1 receptor antagonist (losartan) or
after stimulation with lipopolysaccharide. Blood samples were
obtained from 22 patients with essential hypertension (before any drug
administration or after interruption of antihypertensive therapy) and
from 24 normotensive healthy individuals used as a control group.
Peripheral blood monocytes were isolated by density
gradient centrifugation and plastic adherence. The
state of monocyte activity was determined by the capacity to secrete
tumor necrosis factor-
(TNF-
), interleukin-1ß (IL-1ß), and
interleukin-6, (IL-6) either spontaneously or after stimulation.
Cytokine concentrations were determined in culture supernatants
by specific ELISA. Proinflammatory cytokine levels were
assessed by semiquantitative reverse transcribed polymerase chain
reaction. After stimulation with Ang II, the IL-1ß secretion of
peripheral blood monocytes was significantly increased in
hypertensive patients versus healthy individuals
(P<0.05). In contrast, in monocytes preincubated with
losartan before exposure to Ang II, IL-1ß secretion was
diminished in both groups to comparable levels. The secretion of
IL-1ß and TNF-
was significantly increased in
peripheral blood monocytes from hypertensive patients
versus healthy individuals after stimulation with
lipopolysaccharide (TNF-
, P<0.02; IL-1ß,
P<0.05). Upregulation of IL-1ß and TNF-
secretion
in peripheral blood monocytes from hypertensive patients
was also seen at the RNA level. Our results indicate
preactivated peripheral blood monocytes in
hypertensive patients. Ang II may be directly involved in the process
of monocyte activation.
Key Words: monocytes, human hypertension, essential tumor necrosis factor interleukins polymerase chain reaction angiotensin II
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