on February 7, 2005
Hypertension. 2005
Published online before print February 7, 2005, doi: 10.1161/01.HYP.0000154365.30593.d3
Published online before print February 7, 2005, doi: 10.1161/01.HYP.0000154365.30593.d3
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on October 11, 2004
From CIHR Multidisciplinary Research Group on Hypertension (G.E.C., R.M.T., Y.H., S.M., E.L.S.), Clinical Research Institute of Montreal, University of Montreal, Canada; and the Department of Pharmacology (R.C.T., A.Y.), Institute of Biomedical Sciences, University of Sao Paulo, Brazil. * To whom correspondence should be addressed. E-mail: callereg{at}ircm.qc.ca.
Abstract--Increasing evidence indicates that aldosterone elicits vascular effects through nongenomic signaling pathways. We tested the hypothesis that aldosterone induces activation of vascular mitogen-activated protein (MAP) kinases and NADPH oxidase via c-Src-dependent mechanisms in vascular smooth muscle cells (VSMCs). Aldosterone effects on activation of c-Src, p38MAP kinase, and NADPH oxidase, and incorporation of [3H]proline, an index of collagen synthesis, were assessed in cultured rat VSMCs. Studies were performed in the absence and presence of eplerenone, a selective mineralocorticoid receptor blocker, PP2, a selective Src inhibitor, and SB212190, a selective p38MAPK inhibitor. Phosphorylation of c-Src was dose-dependently increased by aldosterone, with maximal responses obtained at 10-7 mol/L. Aldosterone increased p38MAP kinase phosphorylation, NAD(P)H oxidase activation, and [3H]proline incorporation. These responses were abrogated by eplerenone and almost abolished by PP2. Aldosterone-stimulated incorporation of [3H]proline was significantly reduced by SB212190, indicating that p38MAP kinase plays a role in profibrotic actions of aldosterone. To unambiguously demonstrate the importance of aldosterone in c-Src signaling, VSMCs from c-Src+/+ and c-Src+/- mice were also studied. Aldosterone increased phosphorylation of c-Src, p38MAP kinase, and cortactin, a Src-specific substrate, in c-Src+/+ VSMCs, but not in c-Src-deficient cells. Taken together, our findings demonstrate that nongenomic signaling by aldosterone occurs through c-Src-dependent pathways. These processes may play an important role in profibrotic actions of aldosterone.
Revised on November 4, 2004
Aldosterone Activates Vascular p38MAP Kinase and NADPH Oxidase Via c-Src
Glaucia E. Callera*;
Key words: aldosterone • mineralocorticoids • oxidative stress • vasculature • signal transduction • collagen
This article has been cited by other articles:
 |
|
 |
|
  M. M. Shafiq and A. B. Miller Blocking aldosterone in heart failure Therapeutic Advances in Cardiovascular Disease, October 1, 2009; 3(5): 379 - 385. [Abstract] [PDF]
|
|
|
|
 |
|
 A. Hirata, N. Maeda, A. Hiuge, T. Hibuse, K. Fujita, T. Okada, S. Kihara, T. Funahashi, and I. Shimomura Blockade of mineralocorticoid receptor reverses adipocyte dysfunction and insulin resistance in obese mice Cardiovasc Res, October 1, 2009; 84(1): 164 - 172. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Nakamura, K. Kataoka, M. Fukuda, H. Nako, Y. Tokutomi, Y.-F. Dong, H. Ichijo, H. Ogawa, and S. Kim-Mitsuyama Critical Role of Apoptosis Signal-Regulating Kinase 1 in Aldosterone/Salt-Induced Cardiac Inflammation and Fibrosis Hypertension, September 1, 2009; 54(3): 544 - 551. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Sowers, A. Whaley-Connell, and M. Epstein Narrative Review: The Emerging Clinical Implications of the Role of Aldosterone in the Metabolic Syndrome and Resistant Hypertension Ann Intern Med, June 2, 2009; 150(11): 776 - 783. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Huang, A. Zhang, G. Ding, and R. Chen Aldosterone-induced mesangial cell proliferation is mediated by EGF receptor transactivation Am J Physiol Renal Physiol, June 1, 2009; 296(6): F1323 - F1333. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-G. Wei, Y. Yu, Z.-H. Zhang, and R. B. Felder Angiotensin II upregulates hypothalamic AT1 receptor expression in rats via the mitogen-activated protein kinase pathway Am J Physiol Heart Circ Physiol, May 1, 2009; 296(5): H1425 - H1433. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Wada, S. Ohshima, E. Fujisawa, D. Koya, H. Tsuneki, and T. Sasaoka Aldosterone Inhibits Insulin-Induced Glucose Uptake by Degradation of Insulin Receptor Substrate (IRS) 1 and IRS2 via a Reactive Oxygen Species-Mediated Pathway in 3T3-L1 Adipocytes Endocrinology, April 1, 2009; 150(4): 1662 - 1669. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Goto, F. Otsuka, M. Yamashita, J. Suzuki, H. Otani, H. Takahashi, T. Miyoshi, Y. Mimura, T. Ogura, and H. Makino Enhancement of aldosterone-induced catecholamine production by bone morphogenetic protein-4 through activating Rho and SAPK/JNK pathway in adrenomedullar cells Am J Physiol Endocrinol Metab, April 1, 2009; 296(4): E904 - E916. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Jeong, D. F. Chaupin, K. Matsushita, M. Yamakuchi, S. J. Cameron, C. N. Morrell, and C. J. Lowenstein Aldosterone activates endothelial exocytosis PNAS, March 10, 2009; 106(10): 3782 - 3787. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Yogi, G. E. Callera, R. Tostes, and R. M. Touyz Bradykinin regulates calpain and proinflammatory signaling through TRPM7-sensitive pathways in vascular smooth muscle cells Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2009; 296(2): R201 - R207. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Leroy, S. De Seigneux, V. Agassiz, U. Hasler, M.-E. Rafestin-Oblin, M. Vinciguerra, P.-Y. Martin, and E. Feraille Aldosterone Activates NF-{kappa}B in the Collecting Duct J. Am. Soc. Nephrol., January 1, 2009; 20(1): 131 - 144. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Lopez-Andres, C. Inigo, I. Gallego, J. Diez, and M. A. Fortuno Aldosterone Induces Cardiotrophin-1 Expression in HL-1 Adult Cardiomyocytes Endocrinology, October 1, 2008; 149(10): 4970 - 4978. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.C. Montezano, G.E. Callera, A. Yogi, Y. He, R.C. Tostes, G. He, E.L. Schiffrin, and R.M. Touyz Aldosterone and Angiotensin II Synergistically Stimulate Migration in Vascular Smooth Muscle Cells Through c-Src-Regulated Redox-Sensitive RhoA Pathways Arterioscler Thromb Vasc Biol, August 1, 2008; 28(8): 1511 - 1518. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Zanchi, C. Zoja, M. Morigi, F. Valsecchi, X. Y. Liu, D. Rottoli, M. Locatelli, S. Buelli, A. Pezzotta, P. Mapelli, et al. Fractalkine and CX3CR1 Mediate Leukocyte Capture by Endothelium in Response to Shiga Toxin J. Immunol., July 15, 2008; 181(2): 1460 - 1469. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Sontia, A. C.I. Montezano, T. Paravicini, F. Tabet, and R. M. Touyz Downregulation of Renal TRPM7 and Increased Inflammation and Fibrosis in Aldosterone-Infused Mice: Effects of Magnesium Hypertension, April 1, 2008; 51(4): 915 - 921. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Iwashima, T. Yoshimoto, I. Minami, M. Sakurada, Y. Hirono, and Y. Hirata Aldosterone Induces Superoxide Generation via Rac1 Activation in Endothelial Cells Endocrinology, March 1, 2008; 149(3): 1009 - 1014. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. L. Schiffrin New Twist to the Role of the Renin-Angiotensin System in Heart Failure: Aldosterone Upregulates Renin-Angiotensin System Components in the Brain Hypertension, March 1, 2008; 51(3): 622 - 623. [Full Text] [PDF]
|
|
|
|
|
|
Z.-H. Zhang, Y. Yu, Y.-M. Kang, S.-G. Wei, and R. B. Felder Aldosterone acts centrally to increase brain renin-angiotensin system activity and oxidative stress in normal rats Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H1067 - H1074. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. J. Brown Aldosterone and Vascular Inflammation Hypertension, February 1, 2008; 51(2): 161 - 167. [Full Text] [PDF]
|
|
|
|
|
|
H. Hitomi, H. Kiyomoto, A. Nishiyama, T. Hara, K. Moriwaki, K. Kaifu, G. Ihara, Y. Fujita, T. Ugawa, and M. Kohno Aldosterone Suppresses Insulin Signaling Via the Downregulation of Insulin Receptor Substrate-1 in Vascular Smooth Muscle Cells Hypertension, October 1, 2007; 50(4): 750 - 755. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Yogi, G.E. Callera, A.C.I. Montezano, A.B. Aranha, R.C. Tostes, E.L. Schiffrin, and R.M. Touyz Endothelin-1, but not Ang II, Activates MAP Kinases Through c-Src-Independent Ras-Raf-Dependent Pathways in Vascular Smooth Muscle Cells Arterioscler Thromb Vasc Biol, September 1, 2007; 27(9): 1960 - 1967. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Nietlispach, B. Julius, R. Schindler, A. Bernheim, C. Binkert, W. Kiowski, and H. P. Brunner-La Rocca Influence of Acute and Chronic Mineralocorticoid Excess on Endothelial Function in Healthy Men Hypertension, July 1, 2007; 50(1): 82 - 88. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Otani, F. Otsuka, K. Inagaki, M. Takeda, T. Miyoshi, J. Suzuki, T. Mukai, T. Ogura, and H. Makino Antagonistic effects of bone morphogenetic protein-4 and -7 on renal mesangial cell proliferation induced by aldosterone through MAPK activation Am J Physiol Renal Physiol, May 1, 2007; 292(5): F1513 - F1525. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Hirono, T. Yoshimoto, N. Suzuki, T. Sugiyama, M. Sakurada, S. Takai, N. Kobayashi, M. Shichiri, and Y. Hirata Angiotensin II Receptor Type 1-Mediated Vascular Oxidative Stress and Proinflammatory Gene Expression in Aldosterone-Induced Hypertension: The Possible Role of Local Renin-Angiotensin System Endocrinology, April 1, 2007; 148(4): 1688 - 1696. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Jung, S. L. Marklund, N. Xia, R. Busse, and R. P. Brandes Inactivation of Extracellular Superoxide Dismutase Contributes to the Development of High-Volume Hypertension Arterioscler Thromb Vasc Biol, March 1, 2007; 27(3): 470 - 477. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-K. Park, R. Fischer, R. Dechend, E. Shagdarsuren, A. Gapeljuk, M. Wellner, S. Meiners, P. Gratze, N. Al-Saadi, S. Feldt, et al. p38 Mitogen-Activated Protein Kinase Inhibition Ameliorates Angiotensin II-Induced Target Organ Damage Hypertension, March 1, 2007; 49(3): 481 - 489. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Yu, Y.-M. Kang, Z.-H. Zhang, S.-G. Wei, Y. Chu, R. M. Weiss, and R. B. Felder Increased Cyclooxygenase-2 Expression in Hypothalamic Paraventricular Nucleus in Rats With Heart Failure: Role of Nuclear Factor {kappa}B Hypertension, March 1, 2007; 49(3): 511 - 518. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Gros, Q. Ding, S. Armstrong, C. O'Neil, J. G. Pickering, and R. D. Feldman Rapid effects of aldosterone on clonal human vascular smooth muscle cells Am J Physiol Cell Physiol, February 1, 2007; 292(2): C788 - C794. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Shibata, M. Nagase, S. Yoshida, H. Kawachi, and T. Fujita Podocyte as the Target for Aldosterone: Roles of Oxidative Stress and Sgk1 Hypertension, February 1, 2007; 49(2): 355 - 364. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Bedard and K.-H. Krause The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology Physiol Rev, January 1, 2007; 87(1): 245 - 313. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. M. Thobe, M. Frink, M. A. Choudhry, M. G. Schwacha, K. I. Bland, and I. H. Chaudry Src family kinases regulate p38 MAPK-mediated IL-6 production in Kupffer cells following hypoxia Am J Physiol Cell Physiol, September 1, 2006; 291(3): C476 - C482. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Marumo, H. Uchimura, M. Hayashi, K. Hishikawa, and T. Fujita Aldosterone Impairs Bone Marrow-Derived Progenitor Cell Formation Hypertension, September 1, 2006; 48(3): 490 - 496. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Johar, A. C. Cave, A. Narayanapanicker, D. J. Grieve, and A. M. Shah Aldosterone mediates angiotensin II-induced interstitial cardiac fibrosis via a Nox2-containing NADPH oxidase FASEB J, July 1, 2006; 20(9): 1546 - 1548. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Kobayashi, K. Yoshida, S. Nakano, T. Ohno, T. Honda, Y. Tsubokou, and H. Matsuoka Cardioprotective Mechanisms of Eplerenone on Cardiac Performance and Remodeling in Failing Rat Hearts Hypertension, April 1, 2006; 47(4): 671 - 679. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. L. Schiffrin Effects of Aldosterone on the Vasculature Hypertension, March 1, 2006; 47(3): 312 - 318. [Full Text] [PDF]
|
|
|
|
|
|
K. Miyata, M. Rahman, T. Shokoji, Y. Nagai, G.-X. Zhang, G.-P. Sun, S. Kimura, T. Yukimura, H. Kiyomoto, M. Kohno, et al. Aldosterone Stimulates Reactive Oxygen Species Production through Activation of NADPH Oxidase in Rat Mesangial Cells J. Am. Soc. Nephrol., October 1, 2005; 16(10): 2906 - 2912. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Nagai, K. Miyata, G.-P. Sun, M. Rahman, S. Kimura, A. Miyatake, H. Kiyomoto, M. Kohno, Y. Abe, M. Yoshizumi, et al. Aldosterone Stimulates Collagen Gene Expression and Synthesis Via Activation of ERK1/2 in Rat Renal Fibroblasts Hypertension, October 1, 2005; 46(4): 1039 - 1045. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ishizawa, Y. Izawa, H. Ito, C. Miki, K. Miyata, Y. Fujita, Y. Kanematsu, K. Tsuchiya, T. Tamaki, A. Nishiyama, et al. Aldosterone Stimulates Vascular Smooth Muscle Cell Proliferation Via Big Mitogen-Activated Protein Kinase 1 Activation Hypertension, October 1, 2005; 46(4): 1046 - 1052. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. E. Callera, A. C. I. Montezano, A. Yogi, R. C. Tostes, Y. He, E. L. Schiffrin, and R. M. Touyz c-Src-Dependent Nongenomic Signaling Responses to Aldosterone Are Increased in Vascular Myocytes From Spontaneously Hypertensive Rats Hypertension, October 1, 2005; 46(4): 1032 - 1038. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Wehling Rapid Effects of Aldosterone: Relevant in Cardiac Ischemia? Hypertension, July 1, 2005; 46(1): 27 - 28. [Full Text] [PDF]
|
|
|
|
 |
|
 B. C. Blaxall, J. M. Miano, and B. C. Berk Angiotensin II: A Devious Activator of Mineralocorticoid Receptor-Dependent Gene Expression Circ. Res., April 1, 2005; 96(6): 610 - 611. [Full Text] [PDF]
|
|