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Chronic Toll‐like receptor 9 activation mediates heightened vascular contractility via attenuated NOS activity in isolated aortic segments
Author(s) -
McCarthy Cameron,
Goulopoulou Styliani,
Wenceslau Camilla,
Matsumoto Takayuki,
Webb R. Clinton
Publication year - 2013
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.27.1_supplement.878.6
Subject(s) - nitric oxide synthase , contractility , agonist , chemistry , receptor , medicine , endocrinology , myograph , cyclooxygenase , toll like receptor , nitric oxide , pharmacology , innate immune system , biochemistry , enzyme
Toll‐like receptor 9 (TLR 9) is a pattern recognition receptor of the innate immune system. Activation of TLR 9 in immune cells leads to the release of pro‐inflammatory cytokines. TLR 9 is also expressed in the vasculature; however, its role in vascular function remains to be clarified. We hypothesized that chronic administration (three i.p. injections within five days) of TLR 9 agonist [synthetic oligonucleotide (ODN 2395); 0.1 μg/i.p.], would augment aortic contractility in female, 13–15 weeks old, Sprague Dawley rats. Concentration response curves were performed ex vivo using the myograph to norepinephrine (NE; 10 −9 –3×10 −5 M), in the presence of either nitric oxide synthase (NOS) inhibitor L‐NNA (10 −4 M; 30 min), or cyclooxygenase inhibitor indomethacin (10 −5 M; 30 min). ODN 2395 amplified the contractile response to NE [E max (% max KCl), ODN 2395: 108±4 vs. Veh: 94±5]. This difference was normalized in the presence of L‐NNA [E max (% max KCl), ODN 2395: 141±6 vs. Veh: 134±10], but not indomethacin [E max (% max KCl), ODN 2395: 105±8 vs. Veh: 89±8]. These data illustrate that NOS activity was decreased in the ODN 2395 treated animals, as NOS inhibition normalized the potentiated contractile response to ODN 2395. Therefore, attenuation of NOS activity by TLR 9 activation could subsequently contribute to the development and progression of vascular diseases such as hypertension. Research Support: Society for Women's Health Research (SWHR)