title: Damage-associated molecular pattern activated Toll-like receptor 4 signalling modulates blood pressure in L-NAME-induced hypertension.
abstract: OBJECTIVE
  Recent publications have shed new light on the role of the adaptive and innate immune system in the pathogenesis of hypertension. However, there are limited data whether receptors of the innate immune system may influence blood pressure. Toll-like receptor 4 (TLR4), a pattern recognition receptor, is a key component of the innate immune system, which is activated by exogenous and endogenous ligands. Hypertension is associated with end-organ damage and thus might lead to the release of damage-associated molecular patterns (DAMPs), which are endogenous activators of TLR4 receptors. The present study aimed to elucidate whether TLR4 signalling is able to modulate vascular contractility in an experimental model of hypertension thus contributing to blood pressure regulation.
  
  
  RESULTS
  NG-nitro-l-arginine methyl ester (l-NAME)-induced hypertension was blunted in TLR4(-/-) when compared with wild-type mice. Treatment with l-NAME was associated with a release of DAMPs, leading to reactive oxygen species production of smooth muscle cells in a TLR4-dependent manner. As oxidative stress leads to an impaired function of the NO-sGC-cyclic GMP (cGMP) pathway, we were able to demonstrate that TLR4(-/-) was protected from sGC inactivation. Consequently, arterial contractility was reduced in TLR4(-/-).
  
  
  CONCLUSIONS
  Cell damage-associated TLR4 signalling might act as a direct mediator of vascular contractility providing a molecular link between inflammation and hypertension.
authors.affiliation: Department of Medicine I, Unimedizin Mainz, Johannes Gutenberg University, Langenbeck Str. 1, 55101 Mainz, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sollinger
authors.forename: Ruth
authors.initials: R
authors.lastname: Eißler
authors.forename: Steffen
authors.initials: S
authors.lastname: Lorenz
authors.forename: Susanne
authors.initials: S
authors.lastname: Strand
authors.forename: Stefan
authors.initials: S
authors.lastname: Chmielewski
authors.forename: Cristiane
authors.initials: C
authors.lastname: Aoqui
authors.forename: Christoph
authors.initials: C
authors.lastname: Schmaderer
authors.forename: Hans
authors.initials: H
authors.lastname: Bluyssen
authors.forename: Josef
authors.initials: J
authors.lastname: Zicha
authors.forename: Oliver
authors.initials: O
authors.lastname: Witzke
authors.forename: Elias
authors.initials: E
authors.lastname: Scherer
authors.forename: Jens
authors.initials: J
authors.lastname: Lutz
authors.forename: Uwe
authors.initials: U
authors.lastname: Heemann
authors.forename: Marcus
authors.initials: M
authors.lastname: Baumann
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000293:injuries* / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism*; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000378:metabolism*
chemical_list: C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester
keywords: Hypertension; Innate immunity; Reactive oxygen species; Toll-like receptor; Vascular contractility