Toll-like receptor 4 contributes to blood pressure regulation and vascular contraction in spontaneously hypertensive rats

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

Research output: Contribution to journalArticle

96 Citations (Scopus)

Abstract

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 (cardiovascular 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 TXA 2 (thromboxane A 2) 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.

Original languageEnglish (US)
Pages (from-to)535-543
Number of pages9
JournalClinical Science
Volume122
Issue number11
DOIs
StatePublished - Jun 1 2012

Fingerprint

Toll-Like Receptor 4
Inbred SHR Rats
Blood Vessels
Blood Pressure
Mesenteric Arteries
Immunoglobulin G
Prostaglandin-Endoperoxide Synthases
Wistar Rats
Norepinephrine
Proteins
Toll-Like Receptors
Thromboxanes
Adaptive Immunity
varespladib methyl
Innate Immunity
Hypotension
Anti-Idiotypic Antibodies
Immune System
Interleukin-6
Arterial Pressure

Keywords

  • Cyclo-oxygenase
  • Hypertension
  • Inflammation
  • Mesenteric resistance artery
  • Toll-like receptor 4 (TLR4)

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Bomfim, G. F., dos Santos, R. A., Oliveira, M. A., Giachini, F. R., Akamine, E. H., Tostes, R. C., ... Carvalho, M. H. C. (2012). Toll-like receptor 4 contributes to blood pressure regulation and vascular contraction in spontaneously hypertensive rats. Clinical Science, 122(11), 535-543. https://doi.org/10.1042/CS20110523

Toll-like receptor 4 contributes to blood pressure regulation and vascular contraction in spontaneously hypertensive rats. / Bomfim, Gisele F.; dos Santos, Rosangela A.; Oliveira, Maria Aparecida; Giachini, Fernanda R.; Akamine, Eliana H.; Tostes, Rita C.; Fortes, Zuleica B.; Webb, R Clinton; Carvalho, Maria Helena C.

In: Clinical Science, Vol. 122, No. 11, 01.06.2012, p. 535-543.

Research output: Contribution to journalArticle

Bomfim, GF, dos Santos, RA, Oliveira, MA, Giachini, FR, Akamine, EH, Tostes, RC, Fortes, ZB, Webb, RC & Carvalho, MHC 2012, 'Toll-like receptor 4 contributes to blood pressure regulation and vascular contraction in spontaneously hypertensive rats', Clinical Science, vol. 122, no. 11, pp. 535-543. https://doi.org/10.1042/CS20110523
Bomfim, Gisele F. ; dos Santos, Rosangela A. ; Oliveira, Maria Aparecida ; Giachini, Fernanda R. ; Akamine, Eliana H. ; Tostes, Rita C. ; Fortes, Zuleica B. ; Webb, R Clinton ; Carvalho, Maria Helena C. / Toll-like receptor 4 contributes to blood pressure regulation and vascular contraction in spontaneously hypertensive rats. In: Clinical Science. 2012 ; Vol. 122, No. 11. pp. 535-543.
@article{ae15b07922a64549af0addeefac8f261,
title = "Toll-like receptor 4 contributes to blood pressure regulation and vascular contraction in spontaneously hypertensive rats",
abstract = "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 (cardiovascular 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 TXA 2 (thromboxane A 2) 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.",
keywords = "Cyclo-oxygenase, Hypertension, Inflammation, Mesenteric resistance artery, Toll-like receptor 4 (TLR4)",
author = "Bomfim, {Gisele F.} and {dos Santos}, {Rosangela A.} and Oliveira, {Maria Aparecida} and Giachini, {Fernanda R.} and Akamine, {Eliana H.} and Tostes, {Rita C.} and Fortes, {Zuleica B.} and Webb, {R Clinton} and Carvalho, {Maria Helena C.}",
year = "2012",
month = "6",
day = "1",
doi = "10.1042/CS20110523",
language = "English (US)",
volume = "122",
pages = "535--543",
journal = "Clinical Science",
issn = "0143-5221",
publisher = "Portland Press Ltd.",
number = "11",

}

TY - JOUR

T1 - Toll-like receptor 4 contributes to blood pressure regulation and vascular contraction in spontaneously hypertensive rats

AU - Bomfim, Gisele F.

AU - dos Santos, Rosangela A.

AU - Oliveira, Maria Aparecida

AU - Giachini, Fernanda R.

AU - Akamine, Eliana H.

AU - Tostes, Rita C.

AU - Fortes, Zuleica B.

AU - Webb, R Clinton

AU - Carvalho, Maria Helena C.

PY - 2012/6/1

Y1 - 2012/6/1

N2 - 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 (cardiovascular 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 TXA 2 (thromboxane A 2) 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.

AB - 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 (cardiovascular 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 TXA 2 (thromboxane A 2) 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.

KW - Cyclo-oxygenase

KW - Hypertension

KW - Inflammation

KW - Mesenteric resistance artery

KW - Toll-like receptor 4 (TLR4)

UR - http://www.scopus.com/inward/record.url?scp=84860237455&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84860237455&partnerID=8YFLogxK

U2 - 10.1042/CS20110523

DO - 10.1042/CS20110523

M3 - Article

VL - 122

SP - 535

EP - 543

JO - Clinical Science

JF - Clinical Science

SN - 0143-5221

IS - 11

ER -