Document Detail


Brain microglial cytokines in neurogenic hypertension.
MedLine Citation:
PMID:  20547972     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Accumulating evidence indicates a key role of inflammation in hypertension and cardiovascular disorders. However, the role of inflammatory processes in neurogenic hypertension remains to be determined. Thus, our objective in the present study was to test the hypothesis that activation of microglial cells and the generation of proinflammatory cytokines in the paraventricular nucleus (PVN) contribute to neurogenic hypertension. Intracerebroventricular infusion of minocycline, an anti-inflammatory antibiotic, caused a significant attenuation of mean arterial pressure, cardiac hypertrophy, and plasma norepinephrine induced by chronic angiotensin II infusion. This was associated with decreases in the numbers of activated microglia and mRNAs for interleukin (IL) 1beta, IL-6, and tumor necrosis factor-alpha, and an increase in the mRNA for IL-10 in the PVN. Overexpression of IL-10 induced by recombinant adenoassociated virus-mediated gene transfer in the PVN mimicked the antihypertensive effects of minocycline. Furthermore, acute application of a proinflammatory cytokine, IL-1beta, into the left ventricle or the PVN in normal rats resulted in a significant increase in mean arterial pressure. Collectively, this indicates that angiotensin II induced hypertension involves activation of microglia and increases in proinflammatory cytokines in the PVN. These data have significant implications on the development of innovative therapeutic strategies for the control of neurogenic hypertension.
Authors:
Peng Shi; Carlos Diez-Freire; Joo Yun Jun; Yanfei Qi; Michael J Katovich; Qiuhong Li; Srinivas Sriramula; Joseph Francis; Colin Sumners; Mohan K Raizada
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-06-14
Journal Detail:
Title:  Hypertension     Volume:  56     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-15     Completed Date:  2010-08-10     Revised Date:  2012-01-12    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  297-303     Citation Subset:  IM    
Affiliation:
Department of Physiology and Functional Genomics, University of Florida, Gainesville, FL 32610, USA.
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MeSH Terms
Descriptor/Qualifier:
Angiotensin II / antagonists & inhibitors,  pharmacology
Animals
Anti-Bacterial Agents / pharmacology
Blood Pressure
Brain / drug effects,  metabolism*,  physiopathology
Cytokines / blood,  genetics,  metabolism*
Gene Transfer Techniques
Heart Rate
Immunohistochemistry
Inflammation / physiopathology*
Interleukin-10 / genetics
Interleukin-1beta / genetics
Interleukin-6 / genetics
Male
Microglia / drug effects,  metabolism*
Minocycline / pharmacology
Prosencephalon / drug effects,  metabolism,  physiopathology
RNA, Messenger / genetics
Rats
Rats, Sprague-Dawley
Tumor Necrosis Factor-alpha / genetics
Grant Support
ID/Acronym/Agency:
HL 076803/HL/NHLBI NIH HHS; HL33610/HL/NHLBI NIH HHS; R37 HL033610-25/HL/NHLBI NIH HHS; R37 HL033610-26/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Anti-Bacterial Agents; 0/Cytokines; 0/Interleukin-1beta; 0/Interleukin-6; 0/RNA, Messenger; 0/Tumor Necrosis Factor-alpha; 10118-90-8/Minocycline; 11128-99-7/Angiotensin II; 130068-27-8/Interleukin-10
Comments/Corrections

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