Hypertension augments cardiac Toll-like receptor 4 expression and activity

Ruth Eiler, Christoph Schmaderer, K. Rusai, Louisa Kühne, Daniel Sollinger, Tobias Lahmer, Oliver Witzke, Jens Lutz, Uwe Heemann, Marcus Baumann

Research output: Contribution to journalArticle

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Abstract

Hypertension causes cardiac hypertrophy characterized by low-grade inflammation. Toll-like receptors (TLRs), members of the innate immune system, contribute to cardiac failure. We hypothesized that hypertension is accompanied by enhanced TLR4 expression and activity. Cardiac TLR4 expression was determined in untreated spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY; 4, 8, 16 weeks). Besides, hearts of 8-week-old rats were stimulated with the endogenous TLR4 ligand heparansulfate (HS); the proinflammatory mRNA pattern was assessed (tumor necrosis factor-α (TNF-α), interleukin (IL)-6, monocyte chemotactic protein (MCP)-1). Additionally, we induced hypertension in WKY by L-NAME (N-nitro-L-arginine- methylester hydrochloride). In both hypertension models the effect of ramipril on TLR4 density was assessed. Cardiac TLR4 distribution was investigated by fluorescence-activated cell sorting analysis. Blood pressure (BP) and heart weight/body weight ratio (HW/BW) were elevated in SHR. Constitutive TLR4 expression was augmented in adolescent and adult, but not young SHR compared with WKY. TLR4 staining was pronounced in cardiomyocytes. HS entailed an aggravated TNF-α and IL-6 mRNA response in cardiac tissue, which was significantly pronounced in SHR. Ramipril (10 mg kg 1 per day) reduced BP, HW/BW and TLR4 expression in SHR. L-NAME also augmented TLR4 expression in WKY. Ramipril (1 mg kg-1 per day) lowered BP but TLR4 expression remained unaffected. High-dose ramipril (10 mg kg-1 per day) however decreased TLR4 expression. Starting from adolescence SHR demonstrated enhanced cardiac TLR4 expression. TLR4 was also upregulated in L-NAME induced hypertension. Thus, enhanced TLR4 expression might be linked to the development and maintenance of hypertension. Finally, the antihypertensive, anti-inflammatory action of angiotensin-converting-enzyme inhibition had no effect on TLR4 expression in therapeutic doses but in a high-dose model.

Original languageEnglish
Pages (from-to)551-558
Number of pages8
JournalHypertension Research
Volume34
Issue number5
DOIs
Publication statusPublished - May 2011

Fingerprint

Toll-Like Receptor 4
Inbred SHR Rats
Ramipril
Hypertension
NG-Nitroarginine Methyl Ester
Blood Pressure
Arginine
Interleukin-6
Tumor Necrosis Factor-alpha
Body Weight
Weights and Measures
Messenger RNA
Inbred WKY Rats
Chemokine CCL2
Toll-Like Receptors
Cardiomegaly
Peptidyl-Dipeptidase A
Cardiac Myocytes
Antihypertensive Agents
Young Adult

Keywords

  • cardiac inflammation
  • innate immunity
  • L-NAME
  • RAS inhibition
  • spontaneously hypertensive rat

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Eiler, R., Schmaderer, C., Rusai, K., Kühne, L., Sollinger, D., Lahmer, T., ... Baumann, M. (2011). Hypertension augments cardiac Toll-like receptor 4 expression and activity. Hypertension Research, 34(5), 551-558. https://doi.org/10.1038/hr.2010.270

Hypertension augments cardiac Toll-like receptor 4 expression and activity. / Eiler, Ruth; Schmaderer, Christoph; Rusai, K.; Kühne, Louisa; Sollinger, Daniel; Lahmer, Tobias; Witzke, Oliver; Lutz, Jens; Heemann, Uwe; Baumann, Marcus.

In: Hypertension Research, Vol. 34, No. 5, 05.2011, p. 551-558.

Research output: Contribution to journalArticle

Eiler, R, Schmaderer, C, Rusai, K, Kühne, L, Sollinger, D, Lahmer, T, Witzke, O, Lutz, J, Heemann, U & Baumann, M 2011, 'Hypertension augments cardiac Toll-like receptor 4 expression and activity', Hypertension Research, vol. 34, no. 5, pp. 551-558. https://doi.org/10.1038/hr.2010.270
Eiler, Ruth ; Schmaderer, Christoph ; Rusai, K. ; Kühne, Louisa ; Sollinger, Daniel ; Lahmer, Tobias ; Witzke, Oliver ; Lutz, Jens ; Heemann, Uwe ; Baumann, Marcus. / Hypertension augments cardiac Toll-like receptor 4 expression and activity. In: Hypertension Research. 2011 ; Vol. 34, No. 5. pp. 551-558.
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