IntroductionRenovascular hypertension is the leading cause of secondary hypertension and commonly resistant to antihypertensive therapy. The involvement of toll‐like receptors 9 (TLR9) has already been demonstrated in spontaneously hypertensive rats (SHR) and their activation seems to contribute to the increase in arterial pressure (AP). Therefore, we hypothesized that TLR9 are activated in two‐kidney one‐ clip (2K1C) hypertension, eliciting inflammation and vascular dysfunction, playing a role in the increase of the AP.Methods and ResultsWild type C57BL (WT) and TLR9 knockout (TLR9_KO) mice were anesthetized with isoflurane and were implanted with a silver clip (0.12 mm) around the left renal artery (SHAM operated mice were not implanted with the clip). After 4 weeks, the mice were also anesthetized with isoflurane for direct AP measurement. Afterwards the third‐order mesenteric resistance arteries (MRA) were removed for vascular function evaluation. AP was higher in 2K1C WT mice (133 ± 2 vs 93 ± 4 mmHg in SHAM WT mice), while this increase was partially prevented by the absence of TLR9 (114 ± 5 mmHg in 2K1C TLR9_KO mice). Vascular dysfunction, characterized by increased contractile responses to phenylephrine (Emax: 167 ± 2.2 vs 126 ± 3.5 KCl % in SHAM WT mice) and reduced relaxation to acetylcholine (Emax: 69 ± 1.6 vs 88 ± 1.4 PE % in SHAM WT mice) and sodium nitroprusside (pD2: 7.31 ± 0.07 vs 7.85 ± 0.05 in SHAM WT mice) was found in 2K1C WT mice but not in 2K1C TLR9_KO mice (Emax: 128 ± 2.9 KCl %, 89 ± 2.0 PE % and pD2: 7.78 ± 0.06, when compared to SHAM WT mice, to phenylephrine, acetylcholine and sodium nitroprusside, respectively).ConclusionTLR9 play an important role in vascular dysfunction and AP increase in 2K1C hypertension.Support or Funding InformationFinancial support: FAPESP (Proc. 2015/21976‐1, 2013/20549‐7 and 2016/11988‐5).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.