Document Detail


Toll-like receptor 4 contributes to blood pressure regulation and vascular contraction in spontaneously hypertensive rats.
MedLine Citation:
PMID:  22233532     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Activation of TLRs (Toll-like receptors) induces gene expression of proteins involved in the immune system response. TLR4 has been implicated in the development and progression of CVDs (cardio-vascular diseases). Innate and adaptive immunity contribute to hypertension-associated end-organ damage, although the mechanism by which this occurs remains unclear. In the present study, we hypothesize that inhibition of TLR4 decreases BP (blood pressure) and improves vascular contractility in resistance arteries from SHR (spontaneously hypertensive rats). TLR4 protein expression in mesenteric resistance arteries was higher in 15-week-old SHR than in age-matched Wistar controls or in 5-week-old SHR. To decrease the activation of TLR4, 15-week-old SHR and Wistar rats were treated with anti-TLR4 (anti-TLR4 antibody) or non-specific IgG control antibody for 15 days (1 μg per day, intraperitoneal). Treatment with anti-TLR4 decreased MAP (mean arterial pressure) as well as TLR4 protein expression in mesenteric resistance arteries and IL-6 (interleukin 6) serum levels from SHR when compared with SHR treated with IgG. No changes in these parameters were found in treated Wistar control rats. Mesenteric resistance arteries from anti-TLR4-treated SHR exhibited decreased maximal contractile response to NA (noradrenaline) compared with IgG-treated SHR. Inhibition of COX (cyclo-oxygenase)-1 and COX-2, enzymes related to inflammatory pathways, decreased NA responses only in mesenteric resistance arteries of SHR treated with IgG. COX-2 expression and TXA2 (thromboxane A2) release were decreased in SHR treated with anti-TLR4 compared with IgG-treated SHR. Our results suggest that TLR4 activation contributes to increased BP, low-grade inflammation and plays a role in the augmented vascular contractility displayed by SHR.
Authors:
Gisele F Bomfim; Rosangela A Dos Santos; Maria Aparecida Oliveira; Fernanda R Giachini; Eliana H Akamine; Rita C Tostes; Zuleica B Fortes; R Clinton Webb; Maria Helena C Carvalho
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical science (London, England : 1979)     Volume:  122     ISSN:  1470-8736     ISO Abbreviation:  Clin. Sci.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-02-13     Completed Date:  2012-04-27     Revised Date:  2014-02-03    
Medline Journal Info:
Nlm Unique ID:  7905731     Medline TA:  Clin Sci (Lond)     Country:  England    
Other Details:
Languages:  eng     Pagination:  535-43     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Arteries / physiopathology
Blood Pressure*
Cyclooxygenase 1 / blood
Cyclooxygenase 2 / blood
Epoprostenol / blood
Gene Expression Regulation
Hemodynamics / drug effects
Hypertension / genetics,  physiopathology*
Immunity, Innate
Interleukin-6 / blood
Male
Membrane Proteins / blood
Mesenteric Arteries / metabolism
Rats
Rats, Inbred SHR
Rats, Wistar
Thromboxane A2 / blood
Toll-Like Receptor 4 / antagonists & inhibitors,  immunology,  physiology*
Tumor Necrosis Factor-alpha / blood
Vasoconstriction*
Grant Support
ID/Acronym/Agency:
DK083695/DK/NIDDK NIH HHS; HL071138/HL/NHLBI NIH HHS; R01 DK083685/DK/NIDDK NIH HHS; R01 HL071138/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Interleukin-6; 0/Membrane Proteins; 0/Tlr4 protein, rat; 0/Toll-Like Receptor 4; 0/Tumor Necrosis Factor-alpha; 57576-52-0/Thromboxane A2; DCR9Z582X0/Epoprostenol; EC 1.14.99.1/Cyclooxygenase 1; EC 1.14.99.1/Cyclooxygenase 2; EC 1.14.99.1/Ptgs1 protein, rat; EC 1.14.99.1/Ptgs2 protein, rat

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


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