Document Detail


Brain perivascular macrophages and the sympathetic response to inflammation in rats after myocardial infarction.
MedLine Citation:
PMID:  20142564     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Inflammation is associated with increased sympathetic drive in cardiovascular diseases. Blood-borne proinflammatory cytokines, markers of inflammation, induce cyclooxygenase 2 (COX-2) activity in perivascular macrophages of the blood-brain barrier. COX-2 generates prostaglandin E(2), which may enter the brain and increase sympathetic nerve activity. We examined the contribution of this mechanism to augmented sympathetic drive in rats after myocardial infarction (MI). Approximately 24 hours after acute MI, rats received an intracerebroventricular injection (1 microL/min over 40 minutes) of clodronate liposomes (MI+CLOD) to eliminate brain perivascular macrophages, liposomes alone, or artificial cerebrospinal fluid. A week later, COX-2 immunoreactivity in perivascular macrophages and COX-2 mRNA and protein had increased in hypothalamic paraventricular nucleus of MI rats treated with artificial cerebrospinal fluid or liposomes alone compared with sham-operated rats. In MI+CLOD rats, neither perivascular macrophages nor COX-2 immunoreactivity was seen in the paraventricular nucleus, and COX-2 mRNA and protein levels were similar to those in sham-operated rats. Prostaglandin E(2) in cerebrospinal fluid, paraventricular nucleus neuronal excitation, and plasma norepinephrine were less in MI+CLOD rats than in MI rats treated with artificial cerebrospinal fluid or liposomes alone but more than in sham-operated rats. Intracerebroventricular CLOD had no effect on interleukin 1beta and tumor necrosis factor-alpha mRNA and protein in the paraventricular nucleus or plasma interleukin-1beta and tumor necrosis factor-alpha, which were increased in MI compared with sham-operated rats. In normal rats, pretreatment with intracerebroventricular CLOD reduced (P<0.05) the renal sympathetic, blood pressure, and heart rate responses to intracarotid artery injection of tumor necrosis factor-alpha (0.5 microg/kg); intracerebroventricular liposomes had no effect. The results suggest that proinflammatory cytokines stimulate sympathetic excitation after MI by inducing COX-2 activity and prostaglandin E(2) production in perivascular macrophages of the blood-brain barrier.
Authors:
Yang Yu; Zhi-Hua Zhang; Shun-Guang Wei; Jordi Serrats; Robert M Weiss; Robert B Felder
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2010-02-08
Journal Detail:
Title:  Hypertension     Volume:  55     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-02-19     Completed Date:  2010-03-18     Revised Date:  2011-07-25    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  652-9     Citation Subset:  IM    
Affiliation:
Department of Veterans' Affairs Medical Center, Iowa City, Iowa, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood-Brain Barrier / physiology
Clodronic Acid / pharmacology
Cyclooxygenase 2 / metabolism
Dinoprostone / metabolism
Heart Failure / immunology,  physiopathology
Immunomodulation / physiology
Inflammation / physiopathology*
Injections, Intraventricular
Interleukin-1beta / blood,  genetics
Liposomes / pharmacology
Macrophages / drug effects,  physiology*
Male
Myocardial Infarction / immunology,  physiopathology*
Norepinephrine / blood
Paraventricular Hypothalamic Nucleus / physiology*
RNA, Messenger / metabolism
Rats
Rats, Sprague-Dawley
Sympathetic Nervous System / physiology*
Tumor Necrosis Factor-alpha / blood,  genetics
Grant Support
ID/Acronym/Agency:
R01 HL073986-05A2/HL/NHLBI NIH HHS; R01 HL073986-07/HL/NHLBI NIH HHS; R01HL073986/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Interleukin-1beta; 0/Liposomes; 0/RNA, Messenger; 0/Tumor Necrosis Factor-alpha; 10596-23-3/Clodronic Acid; 363-24-6/Dinoprostone; 51-41-2/Norepinephrine; EC 1.14.99.1/Cyclooxygenase 2
Comments/Corrections
Comment In:
Hypertension. 2010 Mar;55(3):610-1   [PMID:  20142562 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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