Hypertension, Vol 13, 305-314, Copyright © 1989 by American Heart Association
BC Berk, V Vekshtein, HM Gordon and T Tsuda
To investigate the role of vasoconstrictor hormones in vascular smooth
muscle cell growth we have studied the effects of the potent
vasoconstrictor angiotensin II on cell growth in a cultured rat aortic cell
model. Angiotensin II was not mitogenic for these cells, as assessed by
determining cell number, nor was it synergistic in this regard with 10%
calf serum. However, 24-hour exposure to 100 nM angiotensin II caused an
80% increase in protein synthesis (compared with 0.4% increase with serum
control) as measured by tritiated leucine incorporation. This was a
"hypertrophic" response as indicated by a 30% increase in protein content
and a 45% increase in cell volume. Angiotensin II-induced smooth muscle
cell hypertrophy was maximal at 100 nM, had an ED50 of 1 nM, and was
inhibited by the competitive antagonist [Sar1, Ile8]angiotensin II. The
increase in protein synthesis required continuous presence of angiotensin
II for 6 hours and required messenger RNA (mRNA) synthesis as suggested by
complete inhibition after exposure to actinomycin D. Angiotensin
II-stimulated protein synthesis was dependent on a rise in intracellular
Ca2+ concentration evidenced by a 70% decrease in tritiated leucine
incorporation after chelation of Ca2+ with 25 microM quin 2-AM. This
treatment did not alter protein synthesis induced by 10% calf serum.
Decreasing extracellular Na+ to prevent Na+/H+ exchange and intracellular
alkalinization did not inhibit the angiotensin II response but decreased
the 10% calf serum-stimulated protein synthesis by 35%. Downregulation of
protein kinase C by 24-hour treatment with phorbol 12,13-dibutyrate did not
inhibit angiotensin II-induced protein synthesis, while phorbol
12-myristate 13-acetate-stimulated protein synthesis was abolished. These
findings suggest that angiotensin II- induced hypertrophy, acting via a
Ca2+ mechanism, may play an important role in abnormal vascular smooth
muscle cell growth in certain forms of hypertension.
ARTICLES
Angiotensin II-stimulated protein synthesis in cultured vascular smooth muscle cells
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
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N. Fukuda, C. Satoh, W.-Y. Hu, M. Soma, A. Kubo, H. Kishioka, Y. Watanabe, Y. Izumi, and K. Kanmatsuse Production of Angiotensin II by Homogeneous Cultures of Vascular Smooth Muscle Cells From Spontaneously Hypertensive Rats Arterioscler Thromb Vasc Biol, May 1, 1999; 19(5): 1210 - 1217. [Abstract] [Full Text] [PDF]
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G. N. Rao, N. R. Madamanchi, M. Lele, L. Gadiparthi, A.-C. Gingras, T. E. Eling, and N. Sonenberg A Potential Role for Extracellular Signal-regulated Kinases in Prostaglandin F2alpha -induced Protein Synthesis in Smooth Muscle Cells J. Biol. Chem., April 30, 1999; 274(18): 12925 - 12932. [Abstract] [Full Text] [PDF]
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 L. Iouzalen, O. Stepien, and P. Marche Effects of Bay 10-6734 (Embusartan), a New Angiotensin II Type I Receptor Antagonist, on Vascular Smooth Muscle Cell Growth J. Pharmacol. Exp. Ther., April 1, 1999; 289(1): 181 - 187. [Abstract] [Full Text]
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R. D. Smith, A. J. Baukal, P. Dent, and K. J. Catt Raf-1 Kinase Activation by Angiotensin II in Adrenal Glomerulosa Cells: Roles of Gi, Phosphatidylinositol 3-Kinase, and Ca2+ Influx Endocrinology, March 1, 1999; 140(3): 1385 - 1391. [Abstract] [Full Text]
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K. J. Scheidegger, J. Du, and P. Delafontaine Distinct and Common Pathways in the Regulation of Insulin-like Growth Factor-1 Receptor Gene Expression by Angiotensin II and Basic Fibroblast Growth Factor J. Biol. Chem., February 5, 1999; 274(6): 3522 - 3530. [Abstract] [Full Text] [PDF]
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R. Rabbani and E. J. Topol Strategies to achieve coronary arterial plaque stabilization Cardiovasc Res, February 1, 1999; 41(2): 402 - 417. [Abstract] [Full Text] [PDF]
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G. Nickenig, J. Roling, K. Strehlow, P. Schnabel, and M. Bohm Insulin Induces Upregulation of Vascular AT1 Receptor Gene Expression by Posttranscriptional Mechanisms Circulation, December 1, 1998; 98(22): 2453 - 2460. [Abstract] [Full Text] [PDF]
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A. Sabri, G. Govindarajan, T. M. Griffin, K. L. Byron, A. M. Samarel, and P. A. Lucchesi Calcium- and Protein Kinase C–Dependent Activation of the Tyrosine Kinase PYK2 by Angiotensin II in Vascular Smooth Muscle Circ. Res., October 19, 1998; 83(8): 841 - 851. [Abstract] [Full Text] [PDF]
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V. Y. Bogdanov, M. Poon, and M. B. Taubman Platelet-derived Growth Factor-specific Regulation of the JE Promoter in Rat Aortic Smooth Muscle Cells J. Biol. Chem., September 18, 1998; 273(38): 24932 - 24938. [Abstract] [Full Text] [PDF]
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U. Schmitz, T. Ishida, M. Ishida, J. Surapisitchat, M. I. Hasham, S. Pelech, and B. C. Berk Angiotensin II Stimulates p21-Activated Kinase in Vascular Smooth Muscle Cells : Role in Activation of JNK Circ. Res., June 29, 1998; 82(12): 1272 - 1278. [Abstract] [Full Text] [PDF]
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M. Ushio-Fukai, R. W. Alexander, M. Akers, and K. K. Griendling p38 Mitogen-activated Protein Kinase Is a Critical Component of the Redox-sensitive Signaling Pathways Activated by Angiotensin II. ROLE IN VASCULAR SMOOTH MUSCLE CELL HYPERTROPHY J. Biol. Chem., June 12, 1998; 273(24): 15022 - 15029. [Abstract] [Full Text] [PDF]
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E. J. Su, D. M. Lombardi, J. Siegal, and S. M. Schwartz Angiotensin II Induces Vascular Smooth Muscle Cell Replication Independent of Blood Pressure Hypertension, June 1, 1998; 31(6): 1331 - 1337. [Abstract] [Full Text] [PDF]
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P. M. L. Janssen, S. E. Lehnart, J. Prestle, J. C. Lynker, P. Salfeld, H. Just, and G. Hasenfuss The trabecula culture system: a novel technique to study contractile parameters over a multiday time period Am J Physiol Heart Circ Physiol, May 1, 1998; 274(5): H1481 - H1488. [Abstract] [Full Text] [PDF]
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S. Seewald, C. Seul, R. Kettenhofen, D. Bokemeyer, Y. Ko, H. Vetter, and A. Sachinidis Role of Mitogen-Activated Protein Kinase in the Angiotensin II–Induced DNA Synthesis in Vascular Smooth Muscle Cells Hypertension, May 1, 1998; 31(5): 1151 - 1156. [Abstract] [Full Text] [PDF]
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Y.-y. Zhao, D. R. Sawyer, R. R. Baliga, D. J. Opel, X. Han, M. A. Marchionni, and R. A. Kelly Neuregulins Promote Survival and Growth of Cardiac Myocytes. PERSISTENCE OF ErbB2 AND ErbB4 EXPRESSION IN NEONATAL AND ADULT VENTRICULAR MYOCYTES J. Biol. Chem., April 24, 1998; 273(17): 10261 - 10269. [Abstract] [Full Text] [PDF]
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M. B. Hautmann, C. S. Madsen, C. P. Mack, and G. K. Owens Substitution of the Degenerate Smooth Muscle (SM) alpha -Actin CC(A/T-rich)6GG Elements with c-fos Serum Response Elements Results in Increased Basal Expression but Relaxed SM Cell Specificity and Reduced Angiotensin II Inducibility J. Biol. Chem., April 3, 1998; 273(14): 8398 - 8406. [Abstract] [Full Text] [PDF]
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Y. Tian, R. D. Smith, T. Balla, and K. J. Catt Angiotensin II Activates Mitogen-Activated Protein Kinase Via Protein Kinase C and Ras/Raf-1 Kinase in Bovine Adrenal Glomerulosa Cells Endocrinology, April 1, 1998; 139(4): 1801 - 1809. [Abstract] [Full Text] [PDF]
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R. J. Dilley and M. I. Nataatmadja Heparin inhibits mesenteric vascular hypertrophy in angiotensin II-infusion hypertension in rats Cardiovasc Res, April 1, 1998; 38(1): 247 - 255. [Abstract] [Full Text] [PDF]
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 D. S. Damron, H. S. Nadim, S. J. Hong, A. Darvish, and P. A. Murray Intracellular translocation of PKC isoforms in canine pulmonary artery smooth muscle cells by ANG II Am J Physiol Lung Cell Mol Physiol, February 1, 1998; 274(2): L278 - L288. [Abstract] [Full Text] [PDF]
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N. Fukuda, W.-Y. Hu, A. Kubo, M. Endoh, H. Kishioka, C. Satoh, M. Soma, Y. Izumi, and K. Kanmatsuse Abnormal Regulation of Transforming Growth Factor-ß Receptors on Vascular Smooth Muscle Cells From Spontaneously Hypertensive Rats by Angiotensin II Hypertension, February 1, 1998; 31(2): 672 - 677. [Abstract] [Full Text] [PDF]
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M. Ishida, T. Ishida, S. M. Thomas, and B. C. Berk Activation of Extracellular Signal–Regulated Kinases (ERK1/2) by Angiotensin II Is Dependent on c-Src in Vascular Smooth Muscle Cells Circ. Res., January 23, 1998; 82(1): 7 - 12. [Abstract] [Full Text] [PDF]
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N. Ishizaka, R. W. Alexander, J. B. Laursen, H. Kai, T. Fukui, M. Oppermann, R. J. Lefkowitz, P. R. Lyons, and K. K. Griendling G Protein-coupled Receptor Kinase 5 in Cultured Vascular Smooth Muscle Cells and Rat Aorta. REGULATION BY ANGIOTENSIN II AND HYPERTENSION J. Biol. Chem., December 19, 1997; 272(51): 32482 - 32488. [Abstract] [Full Text] [PDF]
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E. Giasson, M. J. Servant, and S. Meloche Cyclic AMP-mediated Inhibition of Angiotensin II-induced Protein Synthesis Is Associated with Suppression of Tyrosine Phosphorylation Signaling in Vascular Smooth Muscle Cells J. Biol. Chem., October 24, 1997; 272(43): 26879 - 26886. [Abstract] [Full Text] [PDF]
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M. B. Hautmann, M. M. Thompson, E. A. Swartz, E. N. Olson, and G. K. Owens Angiotensin II–Induced Stimulation of Smooth Muscle {alpha}-Actin Expression by Serum Response Factor and the Homeodomain Transcription Factor MHox Circ. Res., October 19, 1997; 81(4): 600 - 610. [Abstract] [Full Text]
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R. Higashita, L. Li, V. Van Putten, Y. Yamamura, F. Zarinetchi, L. Heasley, and R. A. Nemenoff Galpha 16 Mimics Vasoconstrictor Action to Induce Smooth Muscle alpha -Actin in Vascular Smooth Muscle Cells through a Jun-NH2-terminal Kinase-dependent Pathway J. Biol. Chem., October 10, 1997; 272(41): 25845 - 25850. [Abstract] [Full Text] [PDF]
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