Journal article
PVN adenovirus-siRNA injections silencing either NOX2 or NOX4 attenuate aldosterone/NaCl-induced hypertension in mice
American journal of physiology. Heart and circulatory physiology, Vol.302(3), pp.H733-H741
02/01/2012
DOI: 10.1152/ajpheart.00873.2011
PMCID: PMC3353786
PMID: 22140041
Abstract
Mineralocorticoid excess increases superoxide production by activating NADPH oxidase (NOX), and intracerebroventricular infusions of NADPH oxidase inhibitors attenuate aldosterone (Aldo)/salt-induced hypertension. It has been hypothesized that increased reactive oxygen species (ROS) in the brain may be a key mechanism in the development of hypertension. The present study investigated the brain regional specificity of NADPH oxidase and the role of NOX2 and NOX4 NADPH oxidase subunits in the hypothalamic paraventricular nucleus (PVN) in Aldo/salt-induced hypertension. PVN injections of adenoviral vectors expressing small interfering (si)RNA targeting NOX2 (AdsiRNA-NOX2) or NOX4 (AdsiRNA-NOX4) mRNAs were used to knock down NOX2 and NOX4 proteins. Three days later, delivery of Aldo (0.2 mg·kg
−1
·day
−1
sc) via osmotic pump commenced and 1% NaCl was provided in place of water. PVN injections of either AdsiRNA-NOX2 or AdsiRNA-NOX4 significantly attenuated the development of Aldo/NaCl-induced hypertension. In an additional study, Aldo/salt-induced hypertension was also significantly attenuated in NOX2 (genomic) knockout mice compared with wild-type controls. When animals from both functional studies underwent ganglionic blockade, there was a reduced fall in blood pressure in the NOX2 and NOX4 knockdown/knockout mice. Western blot analyses of the PVN of siRNA-NOX2- or siRNA-NOX4-injected mice confirmed a marked reduction in the expression of NOX2 or NOX4 protein. In cultured PVN neurons, silencing either NOX2 or NOX4 protein production by culturing PVN cells with siRNA-NOX2 or siRNA-NOX4 attenuated Aldo-induced ROS. These data indicate that both NOX2 and NOX4 in the PVN contribute to elevated sympathetic activity and the hypertensivogenic actions induced by mineralocorticoid excess.
Details
- Title: Subtitle
- PVN adenovirus-siRNA injections silencing either NOX2 or NOX4 attenuate aldosterone/NaCl-induced hypertension in mice
- Creators
- Baojian Xue - Departments of Psychology, Cardiovascular Center, University of Iowa, Iowa City, Iowa; andTerry G Beltz - Departments of PsychologyRalph F Johnson - Departments of PsychologyFang Guo - Departments of PsychologyMeredith Hay - Department of Physiology, University of Arizona, Tucson, ArizonaAlan Kim Johnson - Departments of Psychology, Pharmacology, and Cardiovascular Center, University of Iowa, Iowa City, Iowa; and
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Heart and circulatory physiology, Vol.302(3), pp.H733-H741
- DOI
- 10.1152/ajpheart.00873.2011
- PMID
- 22140041
- PMCID
- PMC3353786
- NLM abbreviation
- Am J Physiol Heart Circ Physiol
- ISSN
- 0363-6135
- eISSN
- 1522-1539
- Publisher
- American Physiological Society
- Grant note
- HL-14388; HL-98207; MH-80241 / National Institutes of Health
- Language
- English
- Date published
- 02/01/2012
- Academic Unit
- Psychological and Brain Sciences; Neuroscience and Pharmacology; Neurology (Pediatrics); Health, Sport, and Human Physiology
- Record Identifier
- 9984213424602771
Metrics
16 Record Views