Genetic study links components of the autonomous nervous system to heart-rate profile during exercise.
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ABSTRACT:
SUBMITTER: Verweij N
PROVIDER: S-EPMC5832790 | biostudies-literature | 2018 Mar
REPOSITORIES: biostudies-literature
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Genetic study links components of the autonomous nervous system to heart-rate profile during exercise.
Verweij Niek N van de Vegte Yordi J YJ van der Harst Pim P
Nature communications 20180301 1
Heart rate (HR) responds to exercise by increasing during exercise and recovering after exercise. As such, HR is an important predictor of mortality that researchers believe is modulated by the autonomic nervous system. However, the mechanistic basis underlying inter-individual differences has yet to be explained. Here, we perform a large-scale genome-wide analysis of HR increase and HR recovery in 58,818 UK Biobank individuals. Twenty-five independent SNPs in 23 loci are identified to be associ ...[more]
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Project description:OBJECTIVES:Glucagon-like peptide-1 (GLP-1) is secreted from enteroendocrine cells and exerts a broad number of metabolic actions through activation of a single GLP-1 receptor (GLP-1R). The cardiovascular actions of GLP-1 have garnered increasing attention as GLP-1R agonists are used to treat human subjects with diabetes and obesity that may be at increased risk for development of heart disease. Here we studied mechanisms linking GLP-1R activation to control of heart rate (HR) in mice. METHODS:The actions of GLP-1R agonists were examined on the control of HR in wild type mice (WT) and in mice with cardiomyocyte-selective disruption of the GLP-1R (Glp1rCM-/-). Complimentary studies examined the effects of GLP-1R agonists in mice co-administered propranolol or atropine. The direct effects of GLP-1R agonism on HR and ventricular developed pressure were examined in isolated perfused mouse hearts ex vivo, and atrial depolarization was quantified in mouse hearts following direct application of liraglutide to perfused atrial preparations ex vivo. RESULTS:Doses of liraglutide and lixisenatide that were equipotent for acute glucose control rapidly increased HR in WT and Glp1rCM-/- mice in vivo. The actions of liraglutide to increase HR were more sustained relative to lixisenatide, and diminished in Glp1rCM-/- mice. The acute chronotropic actions of GLP-1R agonists were attenuated by propranolol but not atropine. Neither native GLP-1 nor lixisenatide increased HR or developed pressure in perfused hearts ex vivo. Moreover, liraglutide had no direct effect on sinoatrial node firing rate in mouse atrial preparations ex vivo. Despite co-localization of HCN4 and GLP-1R in primate hearts, HCN4-directed Cre expression did not attenuate levels of Glp1r mRNA transcripts, but did reduce atrial Gcgr expression in the mouse heart. CONCLUSIONS:GLP-1R agonists increase HR through multiple mechanisms, including regulation of autonomic nervous system function, and activation of the atrial GLP-1R. Surprisingly, the isolated atrial GLP-1R does not transduce a direct chronotropic effect following exposure to GLP-1R agonists in the intact heart, or isolated atrium, ex vivo. Hence, cardiac GLP-1R circuits controlling HR require neural inputs and do not function in a heart-autonomous manner.
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Project description:BackgroundPremature infants may present with damage to the autonomic nervous system (ANS), which may be related to poorer neurological development. Among the techniques used to evaluate the ANS, heart rate variability (HRV) emerged as a simple, non-invasive, and easy to apply tool. The aim of the present study was to analyze and compare HRV in preterm infants at different times of hospitalization in order to verify the possible environmental relationships or clinical evolution with HRV.MethodsA longitudinal, prospective, and descriptive study with non-probabilistic sampling composed of 25 collections of preterm infants of HRV at two moments: moment I (within 15 days of birth) and moment II (after 45 days post-birth). The Polar V800 heart rate monitor was used with the Polar H10 cardiac transducer to collect HRV, which was collected in the supine position for 15 min. The HRV data were analyzed by the linear method in frequency domain and time domain and by the nonlinear method using Kubios HRV analysis software, version 3.0.2.ResultsThere was an increase in HRV values at moment II, these being statistically significant in the SD1, ApEn, and SampEn. Data related to increased sympathetic nervous system activity, parasympathetic nervous system activity, and increased index complexity.ConclusionsThe data demonstrate an increase in HRV values in premature infants at moment II, demonstrating a possible development in the maturation of the ANS during hospitalization.Trial registrationRBR-3x7gz8 retrospectively registered.
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Project description:AIM:Clinical use of glucagon-like peptide-1 receptor agonists (GLP-1RA) is consistently associated with heart rate (HR) acceleration in type 2 diabetes patients. We explored the mechanisms underlying this potential safety concern. METHODS:Ten healthy overweight males (aged 20-27 years) were examined in an open label, crossover study. Automated oscillometric blood pressure measurements and finger photoplethysmography were performed throughout intravenous administration of placebo (saline 0.9%), exenatide (targeting therapeutic concentrations) and a combination of exenatide and the nitric oxide synthase inhibitor L-N(G) -monomethyl arginine (L-NMMA). Sympathetic nervous system (SNS) activity was measured by heart rate variability and rate-pressure product. RESULTS:Exenatide increased HR by a mean maximum of 6.8 (95% CI 1.7, 11.9) beats min(-1) (P < 0.05), systolic blood pressure (SBP) by 9.8 (95% CI 3.5, 16.1) mmHg (P < 0.01) and markers of SNS activity (P < 0.05). No changes in total peripheral resistance were observed. Increases in HR, SBP and sympathetic activity were preserved during concomitant L-NMMA infusion. CONCLUSIONS:Our data argue against exenatide-induced reflex tachycardia as a response to vasodilation and rather suggest the involvement of SNS activation in humans.
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