Published online before print February 7, 2005, doi: 10.1161/01.HYP.0000153463.22621.5e
(Hypertension. 2005;45:717.)
© 2005 American Heart Association, Inc.
Original Articles |
Superoxide Mediates Angiotensin II–Induced Influx of Extracellular Calcium in Neural Cells
From the Department of Anatomy and Cell Biology (M.C.Z., R.V.S., R.L.D.); Free Radical and Radiation Biology Program, Department of Radiation Oncology (M.C.Z., R.L.D.); and The Cardiovascular Center (R.V.S., R.L.D.), The University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City.
Correspondence to Robin L. Davisson, PhD, Department of Anatomy and Cell Biology, 1-418 Bowen Science Building, The University of Iowa College of Medicine, Iowa City, IA 52242. E-mail robin-davisson{at}uiowa.edu
We recently demonstrated that superoxide (O2•–) is a key signaling intermediate in central angiotensin II (Ang II)-elicited blood pressure and drinking responses, and that hypertension caused by systemic Ang II infusion involves oxidative stress in cardiovascular nuclei of the brain. Intracellular Ca2+ is known to play an important role in Ang II signaling in neurons, and it is also linked to reactive oxygen species mechanisms in neurons and other cell types. However, the potential cross-talk between Ang II, O2•–, and Ca2+ in neural cells remains unknown. Using mouse neuroblastoma Neuro-2A cells, we tested the hypothesis that O2•– radicals are involved in the Ang II–induced increase in intracellular Ca2+ concentration ([Ca2+]i) in neurons. Ang II caused a rapid time-dependent increase in [Ca2+]i that was abolished in cells bathed in Ca2+-free medium or by pretreatment with the nonspecific voltage-gated Ca2+ channel blocker CdCl2, suggesting that voltage-sensitive Ca2+ channels are the primary source of Ang II–induced increases in [Ca2+]i in this cell type. Overexpression of cytoplasm-targeted O2•– dismutase via an adenoviral vector (AdCuZnSOD) efficiently scavenged Ang II–induced increases in intracellular O2•– and markedly attenuated the increase in [Ca2+]i caused by this peptide. Furthermore, adenoviral-mediated expression of a dominant-negative isoform of Rac1 (AdN17Rac1), a critical component for NADPH oxidase activation and O2•– production, significantly inhibited the increase in [Ca2+]i after Ang II stimulation. These data provide the first evidence that O2•– is involved in the Ang II–stimulated influx of extracellular Ca2+ in neural cells and suggest a potential intracellular signaling mechanism involved in Ang II–mediated oxidant regulation of central neural control of blood pressure.
Key Words: calcium channels • oxidative stress • imaging • central nervous system • renin-angiotensin system
This article has been cited by other articles:
 |
|
 |
|
  A. Israel, J. Arzola, S. De Jesus, and M. Varela Role of oxidative stress in the natriuresis induced by central administration of angiotensin II Journal of Renin-Angiotensin-Aldosterone System, March 1, 2009; 10(1): 9 - 14. [Abstract] [PDF]
|
|
|
|
 |
|
 G. Wang, T. A. Milner, R. C. Speth, A. C. Gore, D. Wu, C. Iadecola, and J. P. Pierce Sex differences in angiotensin signaling in bulbospinal neurons in the rat rostral ventrolateral medulla Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2008; 295(4): R1149 - R1157. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. M. Sonner, J. A. Filosa, and J. E. Stern Diminished A-type potassium current and altered firing properties in presympathetic PVN neurones in renovascular hypertensive rats J. Physiol., March 15, 2008; 586(6): 1605 - 1622. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Chen and H.-L. Pan Signaling Mechanisms of Angiotensin II-Induced Attenuation of GABAergic Input to Hypothalamic Presympathetic Neurons J Neurophysiol, May 1, 2007; 97(5): 3279 - 3287. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Wang, I. Armando, L. D. Asico, C. Escano, X. Wang, Q. Lu, R. A. Felder, C. G. Schnackenberg, D. R. Sibley, G. M. Eisner, et al. The elevated blood pressure of human GRK4{gamma} A142V transgenic mice is not associated with increased ROS production Am J Physiol Heart Circ Physiol, May 1, 2007; 292(5): H2083 - H2092. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Tolstykh, P. M. de Paula, and S. Mifflin Voltage-Dependent Calcium Currents Are Enhanced in Nucleus of the Solitary Tract Neurons Isolated From Renal Wrap Hypertensive Rats Hypertension, May 1, 2007; 49(5): 1163 - 1169. [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]
|
|
|
|
|
|
I. H. Zucker Novel Mechanisms of Sympathetic Regulation in Chronic Heart Failure Hypertension, December 1, 2006; 48(6): 1005 - 1011. [Full Text] [PDF]
|
|
|
|
|
|
G. Wang, J. Anrather, M. J. Glass, M. J. Tarsitano, P. Zhou, K. A. Frys, V. M. Pickel, and C. Iadecola Nox2, Ca2+, and Protein Kinase C Play a Role in Angiotensin II-Induced Free Radical Production in Nucleus Tractus Solitarius Hypertension, September 1, 2006; 48(3): 482 - 489. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Lu, X. Gong, Y. Lu, J. Guo, C. Wang, and Y. Pan Molecular Cloning and Functional Characterization of a Cell-permeable Superoxide Dismutase Targeted to Lung Adenocarcinoma Cells: INHIBITION CELL PROLIFERATION THROUGH THE Akt/p27kip1 PATHWAY J. Biol. Chem., May 12, 2006; 281(19): 13620 - 13627. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. H. Zucker and L. Gao The Regulation of Sympathetic Nerve Activity by Angiotensin II Involves Reactive Oxygen Species and MAPK Circ. Res., October 14, 2005; 97(8): 737 - 739. [Full Text] [PDF]
|
|
|
|
|
|
S. H.H. Chan, K.-S. Hsu, C.-C. Huang, L.-L. Wang, C.-C. Ou, and J. Y.H. Chan NADPH Oxidase-Derived Superoxide Anion Mediates Angiotensin II-Induced Pressor Effect via Activation of p38 Mitogen-Activated Protein Kinase in the Rostral Ventrolateral Medulla Circ. Res., October 14, 2005; 97(8): 772 - 780. [Abstract] [Full Text] [PDF]
|
|