Abstract 268: Toll-like Receptor 9 (TLR9) Plays a Key Role in the Autonomic Cardiac and Baroreflex Control of Arterial Pressure

Abstract

Introduction: The crosstalk between the immune and nervous system can impact cardiovascular regulation. Toll-like receptor 9 (TLR9) is expressed in immune cells, peripheral nerves and vascular smooth muscle cells. TLR9 is involved in hypertension and cholinergic stimulation suppresses immune responses mediated by TLR9. Based on that, we hypothesized that TLR9 plays a role in cardiac autonomic and baroreflex control of arterial pressure (AP). Methods and Results: TLR9 knockout (KO) and WT mice were anesthetized with isoflurane, implanted with catheters into left carotid artery and right jugular vein and allowed to recovery for 3 days. After basal recording of AP, mice received cardiac autonomic receptor blockers methyl atropine or propranolol. AP and pulse interval (PI) variability were evaluated using the symbolic analysis (non-linear method). Spontaneous baroreflex was evaluated by sequence technique. Mean AP was slightly higher in TLR9 KO (TLR9 KO: 126±2.8 vs WT: 115±4.4 mmHg). In the symbolic analysis the 0V pattern was lower (TLR9 KO: 20±5.4 vs WT: 35±5.0 %) and 2LV pattern was higher in the TLR9 KO (TLR9 KO: 6±1.6 vs WT: 2±0.5 %), an indication of sympathetic and parasympathetic activity, respectively. AP/PI sequences were similar between groups. However, the gain of AP/PI sequences was increased in TLR9 KO (TLR9 KO: 5±1.4 vs WT: 2±0.4 ms/mmHg). Atropine-induced tachycardia was increased in TLR9 KO (TLR9 KO: 23±8.0 vs WT: 2±0.7 ms), whereas propranolol-induced bradycardia was decreased (28±11.0 vs WT: 56±7.6 ms). Conclusions: Our findings demonstrate that TLR9 negatively modulates cardiac vagal tone, and consequently the baroreflex control of AP.