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Toll‐Like Receptor 4 Contributes to Hypertension and Endothelial Dysfunction Produced By Angiotensin II
Author(s) -
Palvia Vijay,
Pyle Chelsea,
Mezzetti Erin,
Chen Xunsheng,
Didion Sean
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.879.5
Subject(s) - endocrinology , angiotensin ii , medicine , tlr4 , endothelial dysfunction , acetylcholine , vasodilation , receptor , renin–angiotensin system , chemistry , endothelium , blood pressure
We have previously found that C3H/He mice are a strain of mice that is resistant to endothelial dysfunction produced by Angiotensin II (Ang II). Interestingly, C3H/He mice carry a point mutation in the Toll‐Like Receptor 4 (TLR4) gene that results in defective TLR4‐mediated signaling. The goal of this study was to further explore the potential role of TLR4 in the hypertension and endothelial dysfunction produced by Ang II. C57Bl/6 (TLR4+/+ strain) and C57Bl/10ScN mice (a strain that carries a null‐mutation for the TLR4 gene) were infused with either vehicle or Ang II (1000 ng/kg/min) for 14 days. Baseline blood pressure was similar in C57Bl/6 and C57Bl/10ScN and on Day 14 of vehicle‐infusion. Ang II‐infusion produced hypertension in both C57Bl/6 and C57Bl/10ScN mice, however the degree of hypertension was significantly greater in C57Bl/6 than C57Bl/10ScN mice (164±6 vs. 147±9 mmHg, respectively). Acetylcholine produced concentration‐dependent relaxation that was similar in carotid arteries from vehicle‐infused C57Bl/6 and C57Bl/10ScN mice. In contrast, responses to acetylcholine were markedly impaired in Ang II‐infused C57Bl/6 mice. Responses to acetylcholine in Ang II‐infused C57Bl/10ScN mice were similar to their vehicle‐infused counterparts. Taken together, these findings demonstrate that TLR4 expression contributes to the hypertension and endothelial dysfunction produced by Ang II.