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(Hypertension. 2000;36:845.)
© 2000 American Heart Association, Inc.
Scientific Contributions |
Angiotensin II Type 2 Receptors Stimulate Collagen Synthesis in Cultured Vascular Smooth Muscle Cells
From the Department of Internal Medicine (M.M., H.S., R.S.-H., T.S.), School of Medicine, Keio University, Tokyo, Japan; and Institute of Applied Biochemistry (H.M.), University of Tsukuba, Ibaraki, Japan.
Correspondence to Hiroyuki Sasamura, MD, PhD, Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. E-mail sasamura{at}mc.med.keio.ac.jp
Abstract—Previously, we and
others have shown that angiotensin II enhances vascular
smooth muscle cell extracellular matrix synthesis via stimulation of
the angiotensin II type 1 (AT1) receptor.
Recently, expression of the type 2 (AT2) receptor has been
confirmed in the adult vasculature, but its role has not yet been fully
defined. The aim of the present study was to examine the effects of
stimulation of AT2 receptors on collagen synthesis in
vascular smooth muscle cells. Retroviral gene transfer was used to
supplement adult vascular smooth muscle cells with AT2
receptors to mimic the vasculature in vivo. The treatment of these
cells with the AT2 receptor agonist CGP42212A
(10-7 mol/L) alone did not cause a significant change in
p42/p44 MAP kinase activity but caused a modest (30% to 50%) decrease
in protein tyrosine phosphatase activity. Treatment with CGP42112A also
caused a dose- and time-dependent increase in both cell-associated and
secretory collagen synthesis (148±17% of control at 48 hours,
P<0.05), which was completely inhibited by the
AT2 receptor antagonist PD123319, unaffected by
the AT1 receptor antagonist losartan,
and attenuated by treatment with pertussis toxin or
G
i antisense
oligonucleotides. Interestingly, studies in other cell
lines demonstrated that CGP42112A caused similar results in transfected
mesangial cells but had essentially opposite effects in
fibroblasts (NIH-3T3-AT2). These results suggest that
AT2 receptor stimulation can increase collagen synthesis in
vascular smooth muscle cells via a
Gi-mediated mechanism and provide evidence
for heterogeneity in the effects of AT2
receptor stimulation in different tissues.
Key Words: angiotensin II • receptor, angiotensin II • collagen • muscle, smooth, vascular • fibroblasts
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