Key result
Blockade of α7nACHR with methyllycaconitine significantly reduced heart rate variability and elicited a febrile response in endotoxemic rats, suggesting a tonic role for these receptors in modulating heart rate dynamics during systemic inflammation.
Why the study?
Does modulation of α7nACHR affect heart rate dynamics and body temperature in endotoxemic rats?
Does modulation of α7nACHR affect heart rate dynamics and body temperature in endotoxemic rats?
p-value: p=<0.01
Nicotinic acetylcholine receptors appear to have a tonic role in modulating heart rate dynamics during systemic inflammation in a rat model of endotoxemia.
May inform autonomic modulation in rodent inflammation models; hypothesis-generating and should not yet change clinical practice in sepsis.
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.
No takes yet. Share an insight, caveat, or question.
Mazloom et al. (2013) studied Endotoxemia. Methyllycaconitine (α7nACHR antagonist) and PHA-543613 (α7nACHR agonist) vs. Saline or LPS alone was evaluated on Heart rate variability (SDNN, SD1, SampEn) (p=<0.01). Blockade of α7nACHR with methyllycaconitine significantly reduced heart rate variability and elicited a febrile response in endotoxemic rats, suggesting a tonic role for these receptors in modulating heart rate dynamics during systemic inflammation.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: