(Hypertension. 2000;36:103.)
© 2000 American Heart Association, Inc.
Scientific Contributions |
Molecular Plasticity of Vascular Wall During NG-Nitro-L-Arginine Methyl Ester–Induced Hypertension
Modulation of Proinflammatory Signals
From INSERM U460, CHU X. Bichat, Paris France, and INSERM U397 (J.-F.A.), CHU Rangueil, Toulouse, France.
Correspondence to Jean-Baptiste Michel, MD, PhD, INSERM U460, Cardiovascular Remodeling, Faculté de Médecine Xavier Bichat, 16, rue H. Huchard, 75018 Paris, France. E-mail u460{at}bichat.inserm.fr
Abstract—It has previously been
reported that hypertension induced by the chronic blockade of NO
production is characterized by a proinflammatory
phenotype of the arterial wall associated with a
periarterial accumulation of inflammatory cells. In the
present study, the cellular and molecular mechanisms involved in
the luminal and perivascular accumulation of inflammatory cells were
evaluated in the aortas of
NG-nitro-L-arginine methyl ester
(L-NAME)–treated rats. Because the medial layer remains intact,
putative markers of the resistance of the vascular wall to cell
migration and to oxidative stress were also explored. For this purpose,
monocyte adhesion, cytokine expression, superoxide anion
production, and nuclear factor-
B (NF-B) activation were
assessed in the aortas of L-NAME–treated rats. Expressions of tissue
inhibitor of metalloproteinases-1 (TIMP-1) and heme
oxygenase-1 (HO-1) in the aortic wall were also studied as
possible markers of such resistance. Chronic blockade of NO
production increased ex vivo monocyte adhesion to the
endothelium, increased the production of
superoxide anions, and activated the NF-B system. In concert
with this modification of the redox state of the vascular wall in
L-NAME–treated rats, the expression of proinflammatory
cytokines interleukin-6, monocyte chemoattractant protein-1,
and macrophage colony–stimulating factor was increased. In
parallel, expressions of both TIMP-1 and HO-1 were increased. All these
changes were prevented by treatment with an
angiotensin-converting enzyme inhibitor
(Zofenopril). Hypertension associated with a proinflammatory
phenotype of the vascular wall induced by blockade of NO
production could be due to an increase in oxidative stress,
which, in turn, activates the NF-B system and increases gene
expression. In parallel, the arterial wall overexpresses
factors such as TIMP-1 and HO-1, which could participate in the
resistance to cell migration and oxidative stress.
Key Words: Keys words: anions • angiotensin-converting enzyme inhibitors • cytokines • matrix metalloproteinases • remodeling
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