title: Toll-like receptor 9 plays a key role in the autonomic cardiac and baroreflex control of arterial pressure.
abstract: 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.
authors: Department of Pharmacology, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, São Paulo, Brazil;
authors: Fernanda Luciano
authors: FL
authors: Rodrigues
authors: Department of Physiology, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, São Paulo, Brazil; and.
authors: Luiz Eduardo V
authors: LE
authors: Silva
authors: Department of Pharmacology, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, São Paulo, Brazil;
authors: Sara Cristina
authors: SC
authors: Hott
authors: Institute of Health Sciences, Federal University of Mato Grosso, Sinop, Mato Grosso, Brazil.
authors: Gisele F
authors: GF
authors: Bomfim
authors: Department of Physiology, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, São Paulo, Brazil; and.
authors: Carlos Alberto Aguiar
authors: CA
authors: da Silva
authors: Department of Physiology, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, São Paulo, Brazil; and.
authors: Rubens
authors: R
authors: Fazan
authors: Department of Pharmacology, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, São Paulo, Brazil;
authors: Leonardo B M
authors: LB
authors: Resstel
authors: Department of Pharmacology, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, São Paulo, Brazil;
authors: Rita C
authors: RC
authors: Tostes
authors: Department of Pharmacology, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, São Paulo, Brazil; fsilvac@usp.br.
authors: Fernando S
authors: FS
authors: Carneiro
mesh_terms: D000818:Animals; D062186:Arterial Pressure; D001286:Atropine Derivatives; D017704:Baroreflex; D001522:Behavior, Animal; D001919:Bradycardia / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D002319:Cardiovascular System / Q000276:immunology / Q000294:innervation*; D003213:Conditioning, Psychological; D004195:Disease Models, Animal; D005239:Fear; D006339:Heart Rate; D007113:Immunity, Innate; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011433:Propranolol; D015398:Signal Transduction; D013610:Tachycardia / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D013997:Time Factors; D051217:Toll-Like Receptor 9 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014630:Vagus Nerve / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D001286:Atropine Derivatives; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; C006649:methylatropine; D011433:Propranolol
keywords: TLR9; parasympathetic nervous system; spontaneous baroreflex