Superoxide mediates the actions of angiotensin II in the central nervous system

Matthew C Zimmerman; Eric Lazartigues; Julie A Lang; Puspha Sinnayah; Iman M Ahmad; Douglas R Spitz; Robin L Davisson

doi:10.1161/01.RES.0000043501.47934.FA

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Superoxide mediates the actions of angiotensin II in the central nervous system

Journal article

Open access

Peer reviewed

Superoxide mediates the actions of angiotensin II in the central nervous system

Matthew C Zimmerman, Eric Lazartigues, Julie A Lang, Puspha Sinnayah, Iman M Ahmad, Douglas R Spitz and Robin L Davisson

Circulation research, Vol.91(11), pp.1038-1045

11/29/2002

DOI: 10.1161/01.RES.0000043501.47934.FA

PMID: 12456490

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Abstract

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.

Angiotensin II - pharmacology

Angiotensin II - physiology

Animals

Blood Pressure - drug effects

Blood Pressure - physiology

Cells, Cultured

Central Nervous System - drug effects

Central Nervous System - metabolism

Drinking Behavior - drug effects

Drinking Behavior - physiology

Genetic Vectors - administration & dosage

Genetic Vectors - genetics

Humans

Hypothalamus - cytology

Hypothalamus - drug effects

Hypothalamus - metabolism

Injections, Intra-Arterial

Injections, Intraventricular

Mice

Mice, Inbred C57BL

Mitochondria - enzymology

Muscarinic Agonists - pharmacology

Rats

Rats, Sprague-Dawley

Signal Transduction - drug effects

Signal Transduction - physiology

Superoxide Dismutase - genetics

Superoxide Dismutase - metabolism

Superoxide Dismutase - pharmacology

Superoxides - metabolism

Transgenes

Details

Title: Subtitle: Superoxide mediates the actions of angiotensin II in the central nervous system
Creators: Matthew C Zimmerman - University of Iowa
Eric Lazartigues - Roy J. and Lucille A. Carver College of Medicine
Julie A Lang - Roy J. and Lucille A. Carver College of Medicine
Puspha Sinnayah - Roy J. and Lucille A. Carver College of Medicine
Iman M Ahmad - Roy J. and Lucille A. Carver College of Medicine
Douglas R Spitz - Roy J. and Lucille A. Carver College of Medicine
Robin L Davisson - Roy J. and Lucille A. Carver College of Medicine
Resource Type: Journal article
Publication Details: Circulation research, Vol.91(11), pp.1038-1045
DOI: 10.1161/01.RES.0000043501.47934.FA
PMID: 12456490
ISSN: 0009-7330
eISSN: 1524-4571
Grant note: 5T32 CA78586 / NCI NIH HHS HL-63887 / NHLBI NIH HHS HL-14388 / NHLBI NIH HHS CA-66081 / NCI NIH HHS HL-51469 / NHLBI NIH HHS
Language: English
Date published: 11/29/2002
Academic Unit: Pathology; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center
Record Identifier: 9984313085702771

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