title: The role of α7 nicotinic acetylcholine receptor in modulation of heart rate dynamics in endotoxemic rats.
abstract: Previous reports have indicated that artificial stimulation of the vagus nerve reduces systemic inflammation in experimental models of sepsis. This phenomenon is a part of a broader cholinergic anti-inflammatory pathway which activates the vagus nerve to modulate inflammation through activation of alpha7 nicotinic acetylcholine receptors (α7nACHR). Heart rate variability represents the complex interplay between autonomic nervous system and cardiac pacemaker cells. Reduced heart rate variability and increased cardiac cycle regularity is a hallmark of clinical conditions that are associated with systemic inflammation (e.g. endotoxemia and sepsis). The present study was aimed to assess the role of α7nACHR in modulation of heart rate dynamics during systemic inflammation. Systemic inflammation was induced by injection of endotoxin (lipopolysaccharide) in rats. Electrocardiogram and body temperature were recorded in conscious animals using a telemetric system. Linear and non-linear indices of heart rate variability (e.g. sample entropy and fractal-like temporal structure) were assessed. RT-PCR and immunohistochemistry studies showed that α7nACHR is expressed in rat atrium and is mainly localized at the endothelial layer. Systemic administration of an α7nACHR antagonist (methyllycaconitine) did not show a significant effect on body temperature or heart rate dynamics in naïve rats. However, α7nACHR blockade could further reduce heart rate variability and elicit a febrile response in endotoxemic rats. Pre-treatment of endotoxemic animals with an α7nACHR agonist (PHA-543613) was unable to modulate heart rate dynamics in endotoxemic rats but could prevent the effect of endotoxin on body temperature within 24 h experiment. Neither methyllycaconitine nor PHA-543613 could affect cardiac beating variability of isolated perfused hearts taken from control or endotoxemic rats. Based on our observations we suggest a tonic role for nicotinic acetylcholine receptors in modulation of heart rate dynamics during systemic inflammation.
authors: Department of Physiology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors: Roham
authors: R
authors: Mazloom
authors: Golnar
authors: G
authors: Eftekhari
authors: Maryam
authors: M
authors: Rahimi-Balaei
authors: Maryam
authors: M
authors: Rahimi
authors: Vahid
authors: V
authors: Khori
authors: Sohrab
authors: S
authors: Hajizadeh
authors: Ahmad R
authors: AR
authors: Dehpour
authors: Ali R
authors: AR
authors: Mani
mesh_terms: D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D019446:Endotoxemia / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology*; D006325:Heart Atria / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D011812:Quinuclidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000819:agonists / Q000096:biosynthesis
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D008070:Lipopolysaccharides; C513163:N-(1-azabicyclo(2.2.2)oct-3-yl)furo(2,3-c)pyridine-5-carboxamide; D011812:Quinuclidines; D064569:alpha7 Nicotinic Acetylcholine Receptor