From the Second Department of Internal Medicine, Nihon University School
of Medicine, Tokyo, Japan.
Correspondence to Noboru Fukuda, MD, Second Department of Internal Medicine, Nihon University School of Medicine, Ooyaguchi-kami 30-1, Itabashi-ku, Tokyo 173, Japan.
AbstractThe effects of angiotensin II (Ang II)
on the expression and characteristics of transforming growth factor-ß
(TGF-ß) receptors on vascular smooth muscle cells (VSMC) from
Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) were
investigated. TGF-ßinduced stimulation of DNA synthesis by VSMC
from WKY rats was abolished with Ang II, whereas basal and
TGF-ßstimulated DNA synthesis by VSMC from SHR was increased with
Ang II. Ang II stimulated DNA synthesis by VSMC from WKY rats in the
presence but not in the absence of neutralizing antibody to
TGF-ß1. Antibody to TGF-ß1 enhanced the
stimulatory effect of Ang II on DNA synthesis by VSMC from SHR. Ang II
increased the specific binding of TGF-ß to VSMC from WKY rats by
increasing both the expression of the lower-affinity of TGF-ß
receptors as well as the total number of TGF-ß binding sites. In
contrast, VSMC from SHR showed a higher affinity and number of TGF-ß
receptors in the absence of Ang II than did cells from WKY rats, and
these parameters were not affected by Ang II. Ang II
increased the expression of TGF-ß type I receptor mRNA in VSMC from
WKY rats but had no effect of TGF-ß receptor type I or II mRNA in
VSMC from SHR, which predominantly express the type II receptor. These
results indicate that an increase in the expression of the TGF-ß type
I receptor by Ang II may facilitate the ability of
endogenous TGF-ß to counteract the stimulatory effect of
Ang II on growth in VSMC from WKY rats, whereas endogenous
TGF-ß induced by Ang II cannot counteract the growth-promoting action
of Ang II in VSMC from SHR. The abnormal regulation of TGF-ß
receptors by Ang II may be associated with the exaggerated growth of
VSMC from SHR.
© 1998 American Heart Association, Inc.
Scientific Contributions
Abnormal Regulation of Transforming Growth Factor-ß Receptors on Vascular Smooth Muscle Cells From Spontaneously Hypertensive Rats by Angiotensin II
Key Words: angiotensin II transforming growth factors receptors vascular smooth muscle rats, inbred SHR
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