(Hypertension. 2001;37:58.)
© 2001 American Heart Association, Inc.
Scientific Contributions |
Upregulated Expression of Rat Heart Intercellular Adhesion Molecule-1 in Angiotensin II– but Not Phenylephrine- Induced Hypertension
From the Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, Mich.
Correspondence to Patrick J. Pagano, PhD, Hypertension and Vascular Research Division, Henry Ford Hospital, 2799 West Grand Blvd, Detroit, MI 48202. E-mail ppagano1{at}hfhs.org
Abstract—Intercellular adhesion
molecule-1 (ICAM-1), part of an immunoglobulin-like superfamily of
adhesion molecules, is involved in several
cardiovascular diseases. We investigated whether in
vivo angiotensin II (Ang II) increases ICAM-1 in rats.
Sprague-Dawley rats were infused with vehicle or Ang II (750 µg
· kg-1 · d-1 SC) for 7 days. The
contribution of Ang II receptors to ICAM-1 expression was investigated
with a nonpeptide Ang II type 1 (AT1) receptor
antagonist losartan (30 mg · kg-1
· d-1 in drinking water). Systolic blood
pressure was elevated in Ang II–treated animals compared with
sham-treated controls, and losartan blocked this increase.
Tumor necrosis factor (TNF)-
(5 µg/kg IP bolus), a prototype
inducer of ICAM-1, was administered as a positive control for ICAM-1
expression. After treatment, hearts were frozen in liquid nitrogen;
homogenates were subjected to SDS-PAGE and
immunoblotted with an anti-rat ICAM-1 monoclonal antibody.
We detected a predominantly high-molecular-weight band in
homogenates from non–TNF-–treated rats, which was
enhanced by 80±5% in TNF-–treated rats. This band measured 
200
kDa, which is the molecular weight of ICAM-1 in its native dimer form.
The same band was detected in homogenates from sham and Ang
II–treated rats, with the latter showing a 150±10% increase in
ICAM-1 versus sham controls. Immunoprecipitation of rat heart
homogenates with anti-rat ICAM-1 antibody resulted in a
dominant band of the same molecular weight as samples not treated with
antibody. Losartan prevented enhanced expression of ICAM-1 in
the presence of Ang II but had no effect on basal ICAM-1 expression.
Phenylephrine, an -agonist (3 mg ·
kg-1 · d-1 ), was infused for 1 week
but had no effect on ICAM-1 expression, even though systolic
blood pressure was elevated to the same level as in rats treated with
Ang II. Thus, heart ICAM-1 expression is enhanced via AT1
receptor activation independent of hypertension. Ang II–induced ICAM-1
expression was time and dose dependent, with maximal expression
occurring within 5 to 7 days at 100 to 750 µg/kg Ang II.
Immunohistochemical staining demonstrated markedly increased ICAM-1
levels in the perivascular area in Ang II–infused rats.
Monocyte/macrophage accumulation was significantly greater in
Ang II–treated rat hearts than in sham-treated hearts (10±1;
P<0.001; n=5). Thus during inflammation, overexpression
of ICAM-1 may contribute to cardiovascular damage in
diseases characterized by increased activity of the
renin-angiotensin system.
Key Words: angiotensin II • cell adhesion molecules • hypertension, experimental • losartan • phenylephrine
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