Angiotensin ii type 1 receptor-mediated activation of ras in
cultured rat vascular smooth muscle cells.
Okuda, Masanori, Yasuhiro Kawahara, and Mitsuhiro Yokoyama.
Department of Internal Medicine (1st Division), Kobe University
School of Medicine, Kobe 650, Japan
APStracts 3:0067H, 1996.
Angiotensin II (Ang II), a potent growth promoting factor of vascular
smooth muscle cells (VSMC), induces activation of MAP kinases and
subsequent expression of the c-fos proto-oncogene in VSMC. However,
it remains obscure whether Ang II induces activation of the ras
proto-oncogene product (Ras) and, if it does, whether Ras is involved
in signaling from the Ang II receptor to the MAP kinase pathway in
VSMC. In cultured VSMC, Ang II activated Ras comparably to epidermal
growth factor. Ang II-induced Ras activation was detectable within 1
min and maximal at 2-5 minutes. The Ang II type 1 (AT1) receptor
antagonist, CV-11974, completely inhibited this reaction. Pertussis
toxin treatment of VSMC inhibited Ang II-induced Ras activation by
about 70%, but it had no effect on Ang II-induced MAP kinase
activation and c-fos expression. These results indicate that Ang II
activates Ras via AT1 receptors which are predominantly linked to a G
protein of the Gi subfamily in VSMC and suggest that Ras activation
may not be a prerequisite for Ang II-induced MAP kinase activation
and c-fos expression in this cell type.
Received 15 November 1995; accepted in final form 24 January
1996.
APS Manuscript Number H1074-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 14 February 96