Mice lacking the gene for Toll Like receptor‐4 (TLR4) had an attenuated blood pressure response to Angiotensin II infusion

Abstract

Hypertension (HTN) is considered as a low grade inflammatory disease. Previous studies from our lab indicate that brain inflammatory molecules contribute to the development of HTN. Since TLR4 is a major modulator of inflammation, in this study, we explored the role of TLR4 in angiotensin II (ANGII) induced HTN. TLR4 knock‐out (KO) and wild type (WT) mice were implanted with telemetry probes for mean arterial pressure (MAP) measurements. After collecting baseline MAP, osmotic minipump containing ANGII (200ng/kg/min) or saline was implanted for 14 days. Then the brains microdissected for the paraventricular nucleus (PVN), sub fornical organ (SFO), nucleus tractus solatorius (NTS) and ventrolateral medulla (VLM) and examined for the expression of prorenin receptor (PRR) and interleukin(IL)‐1β by RT‐PCR. In WT mice, ANG II infusion increased MAP by day 3 (122±4) and peaked on day 9 (145±2) and remained elevated. This was accompanied by an increase in IL‐1β and PRR in the SFO, PVN, VLM and NTS. In contrast, ANGII infusion in TLR4 KO did not increase MAP (96±2) and remained lower (97±2) when compared with WT+ANGII (144±3). In addition, there was decrease in the expression of PRR and IL‐1β in the brain regions of TLR4 KO after ANGII. These finding indicate that ANGII induced HTN is at least in part mediated by TLR4 expression in the pressor regions of the brain and is associated with increase in PRR and IL‐1β expression. Funding: LSU