Circulation Research. 2002;91:1038-1045
Published online before print October 24, 2002, doi: 10.1161/01.RES.0000043501.47934.FA
Published online before print October 24, 2002, doi: 10.1161/01.RES.0000043501.47934.FA
© 2002 American Heart Association, Inc.
Integrative Physiology |
Superoxide Mediates the Actions of Angiotensin II in the Central Nervous System
From the Department of Anatomy and Cell Biology (M.C.Z., E.L., J.A.L., P.S., R.L.D.) and the Free Radical and Radiation Biology Program, Department of Radiation Oncology (M.C.Z., I.M.A., D.R.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, 1-251 Bowen Science Building, The University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242. E-mail robin-davisson{at}uiowa.edu
Angiotensin II (Ang II) has profound effects in the central nervous system (CNS), including promotion of thirst, regulation of vasopressin secretion, and modulation of sympathetic outflow. Despite its importance in cardiovascular and volume homeostasis, angiotensinergic mechanisms are incompletely understood in the CNS. Recently, a novel signaling mechanism for Ang II involving reactive oxygen species (ROS) has been identified in a variety of peripheral tissues, but the involvement of ROS as second messengers in Ang II–mediated signaling in the CNS has not been reported. The hypothesis that superoxide is a key mediator of the actions of Ang II in the CNS was tested in mice using adenoviral vector–mediated expression of superoxide dismutase (AdSOD). Changes in blood pressure, heart rate, and drinking elicited by injection of Ang II in the CNS were abolished by prior treatment with AdSOD in the brain, whereas the cardiovascular responses to carbachol, another central vasopressor agent, were unaffected. In addition, Ang II stimulated superoxide generation in primary CNS cell cultures, and this was prevented by the Ang II receptor (Ang II type 1 subtype) antagonist losartan or AdSOD. These results identify a novel signaling mechanism mediating the actions of Ang II in the CNS. Dysregulation of this signaling cascade may be important in hypertension and heart failure triggered by Ang II acting in the CNS.
Key Words: blood pressure • thirst • reactive oxygen species • renin-angiotensin system • brain
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|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
C. Sun, K. W. Sellers, C. Sumners, and M. K. Raizada NAD(P)H Oxidase Inhibition Attenuates Neuronal Chronotropic Actions of Angiotensin II Circ. Res., April 1, 2005; 96(6): 659 - 666. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
M. C. Zimmerman, E. Lazartigues, R. V. Sharma, and R. L. Davisson Hypertension Caused by Angiotensin II Infusion Involves Increased Superoxide Production in the Central Nervous System Circ. Res., July 23, 2004; 95(2): 210 - 216. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 T. M. Buetler, A. Krauskopf, and U. T. Ruegg Role of Superoxide as a Signaling Molecule Physiology, June 1, 2004; 19(3): 120 - 123. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Dai, J. J. Galligan, S. W. Watts, G. D. Fink, and D. L. Kreulen Increased O2{middle dot}- Production and Upregulation of ETB Receptors by Sympathetic Neurons in DOCA-Salt Hypertensive Rats Hypertension, May 1, 2004; 43(5): 1048 - 1054. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. E. Lindley, M. F. Doobay, R. V. Sharma, and R. L. Davisson Superoxide Is Involved in the Central Nervous System Activation and Sympathoexcitation of Myocardial Infarction-Induced Heart Failure Circ. Res., February 20, 2004; 94(3): 402 - 409. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. C. Kopp and M. Z. Cicha Impaired substance P release from renal sensory nerves in SHR involves a pertussis toxin-sensitive mechanism Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2004; 286(2): R326 - R333. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Francis, T. Beltz, A. K. Johnson, and R. B. Felder Mineralocorticoids act centrally to regulate blood-borne tumor necrosis factor-{alpha} in normal rats Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2003; 285(6): R1402 - R1409. [Abstract] [Full Text] [PDF] |