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

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Fernanda L Rodrigues ◽  
Gisele F Bomfim ◽  
Carlos A Silva ◽  
Rubens Fazan ◽  
Rita C Tostes ◽  
...  

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.

2015 ◽  
Vol 308 (8) ◽  
pp. R714-R723 ◽  
Author(s):  
Fernanda Luciano Rodrigues ◽  
Luiz Eduardo V. Silva ◽  
Sara Cristina Hott ◽  
Gisele F. Bomfim ◽  
Carlos Alberto Aguiar da Silva ◽  
...  

The crosstalk between the immune and the autonomic nervous system may impact the cardiovascular function. Toll-like receptors are components of the innate immune system and play developmental and physiological roles. Toll-like receptor 9 (TLR9) is involved in the pathogenesis of cardiovascular diseases, such as hypertension and heart failure. Since such diseases are commonly accompanied by autonomic imbalance and lower baroreflex sensitivity, we hypothesized that TLR9 modulates cardiac autonomic and baroreflex control of arterial pressure (AP). Toll-like receptor 9 knockout (TLR9 KO) and wild-type (WT) mice were implanted with catheters into carotid artery and jugular vein and allowed to recover for 3 days. After basal recording of AP, mice received methyl-atropine or propranolol. AP and pulse interval (PI) variability were evaluated in the time and frequency domain (spectral analysis), as well as by multiscale entropy. Spontaneous baroreflex was studied by sequence technique. Behavioral and cardiovascular responses to fear-conditioning stress were also evaluated. AP was similar between groups, but TLR9 KO mice exhibited lower basal heart rate (HR). AP variability was not different, but PI variability was increased in TLR9 KO mice. The total entropy was higher in TLR9 KO mice. Moreover, baroreflex function was found higher in TLR9 KO mice. Atropine-induced tachycardia was increased in TLR9 KO mice, whereas the propranolol-induced bradycardia was similar to WT mice. TLR9 KO mice exhibit increased behavioral and decreased tachycardia responses to fear-conditioning stress. In conclusion, our findings suggest that TLR9 may negatively modulate cardiac vagal tone and baroreflex in mice.


Author(s):  
Mathias Baumert ◽  
Michal Javorka ◽  
Muammar Kabir

Beat-to-beat variations in heart period provide information on cardiovascular control and are closely linked to variations in arterial pressure and respiration. Joint symbolic analysis of heart period, systolic arterial pressure and respiration allows for a simple description of their shared short-term dynamics that are governed by cardiac baroreflex control and cardiorespiratory coupling. In this review, we discuss methodology and research applications. Studies suggest that analysis of joint symbolic dynamics provides a powerful tool for identifying physiological and pathophysiological changes in cardiovascular and cardiorespiratory control.


2008 ◽  
Vol 294 (1) ◽  
pp. R142-R150 ◽  
Author(s):  
Dominique Laude ◽  
Véronique Baudrie ◽  
Jean-Luc Elghozi

Short-term blood pressure (BP) variability is limited by the arterial baroreflex. Methods for measuring the spontaneous baroreflex sensitivity (BRS) aim to quantify the gain of the transfer function between BP and pulse interval (PI) or the slope of the linear relationship between parallel BP and PI changes. These frequency-domain (spectral) and time-domain (sequence) techniques were tested in conscious mice equipped with telemetric devices. The autonomic relevance of these indexes was evaluated using pharmacological blockades. The significant changes of the spectral bandwidths resulting from the autonomic blockades were used to identify the low-frequency (LF) and high-frequency (HF) zones of interest. The LF gain was 1.45 ± 0.14 ms/mmHg, with a PI delay of 0.5 s. For the HF gain, the average values were 2.0 ± 0.19 ms/mmHg, with a null phase. LF and HF bands were markedly affected by atropine. On the same 51.2-s segments used for cross-spectral analysis, an average number of 26.4 ± 2.2 slopes were detected, and the average slope in resting mice was 4.4 ± 0.5 ms/mmHg. Atropine significantly reduced the slopes of the sequence method. BRS measurements obtained using the sequence technique were highly correlated to the spectral estimates. This study demonstrates the applicability of the recent methods used to estimate spontaneous BRS in mice. There was a vagal predominance in the baroreflex control of heart rate in conscious mice in the present conditions.


1982 ◽  
Vol 243 (1) ◽  
pp. R18-R24 ◽  
Author(s):  
R. Y. Chen ◽  
F. C. Fan ◽  
G. B. Schuessler ◽  
S. Chien

The baroreflex control of heart rate was investigated on 10 informed human subjects during light halothane anesthesia (0.3-0.5%, inspired concentration). The relationship of systolic pressure (SP) to the succeeding pulse interval (PI) was evaluated on a beat-to-beat basis during the entire course of sodium nitroprusside (SNP) depressor test. The initial slope of SP-PI plot (dPI/dSP) was used as an index of the sensitivity of baroreflex control of heart rate. Following an injection of SNP (4-6 micrograms/kg), dPI/dt was related directly to dPI/dSP, whereas the latter was inversely correlated with dSP/dt. The recovery of PI lagged behind that of SP, and there was a hysteresislike loop on the SP-PI plot. The time lag of PI recovery and the loop of SP-PI plot were markedly decreased by propranolol treatment and significantly increased by atropine. The slopes of SP-PI plot were significantly decreased by atropine but relatively unaffected by propranolol. These results indicate that SNP-induced hypotension in man during halothane anesthesia is associated with a withdrawal of parasympathetic inhibition and an enhancement of sympathetic activity. The autonomic control of heart rate in response to rapid changes in arterial pressure induced by SNP is dominated by parasympathetic influence; the more persistent sympathetic activity only becomes evident when the parasympathetic influence subsides quickly as the arterial pressure stays relatively constant at a new level. The slope of SP-PI plot (dPI/dSP) and the ratio of dPI/dt to dSP/dt during the decreasing pressure phase of SNP test can be used as indices for the sensitivity of baroreflex control of heart rate.


2003 ◽  
Vol 95 (5) ◽  
pp. 1789-1798 ◽  
Author(s):  
Kichang Lee ◽  
Dwayne N. Jackson ◽  
Douglas L. Cordero ◽  
Takeshi Nishiyasu ◽  
Jochen K. Peters ◽  
...  

Spontaneous baroreflex control of pulse interval (PI) was assessed in healthy volunteers under thermoneutral and heat stress conditions. Subjects rested in the supine position with their lower legs in a water bath at 34°C. Heat stress was imposed by increasing the bath temperature to 44°C. Arterial blood pressure (Finapres), PI (ECG), esophageal and skin temperature, and stroke volume were continuously collected during each 5-min experimental stage. Spontaneous baroreflex function was evaluated by multiple techniques, including 1) the mean slope of the linear relationship between PI and systolic blood pressure (SBP) with three or more simultaneous increasing or decreasing sequences, 2) the linear relationship between changes in PI and SBP (ΔPI/ΔSBP) derived by using the first differential equation, 3) the linear relationship between changes in PI and SBP with simultaneously increasing or decreasing sequences (+ΔPI/+ΔSBP or -ΔPI/-ΔSBP), and 4) transfer function analysis. Heat stress increased esophageal temperature by 0.6 ± 0.1°C, decreased PI from 1,007 ± 43 to 776 ± 37 ms and stroke volume by 16 ± 5 ml/beat. Heat stress reduced baroreflex sensitivity but increased the incidence of baroreflex slopes from 5.2 ± 0.8 to 8.6 ± 0.9 sequences per 100 heartbeats. Baroreflex sensitivity was significantly correlated with PI or vagal power ( r2 = 0.45, r2 = 0.71, respectively; P < 0.05). However, the attenuation in baroreflex sensitivity during heat stress appeared related to a shift in autonomic balance (shift in resting PI) rather than heat stress per se.


1978 ◽  
Vol 55 (s4) ◽  
pp. 381s-382s ◽  
Author(s):  
P. Sleight ◽  
P. Fox ◽  
R. Lopez ◽  
D. E. Brooks

1. Baroreflex sensitivity was tested in three normal, three borderline and one hypertensive subject before and during mental arithmetic, the prolongation of pulse interval caused by a provoked rise in blood pressure being used as a measure of baroreflex sensitivity. 2. Baroreflex sensitivity was significantly decreased during mental arithmetic. 3. During mental arithmetic the arterial pressure fluctuated markedly. 4. These findings suggest that in man, as well as animals, the defence of alerting reaction depresses baroreflex control and thus contributes to the rise in blood pressure seen at this time.


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