Home About us Contact
|
Home About us Contact | ||
|
|
||
Pharmacological Modulation (pharmacological + modulation)
Selected AbstractsActivation of the transient receptor potential vanilloid-1 (TRPV1) channel opens the gate for pain reliefBRITISH JOURNAL OF PHARMACOLOGY, Issue 8 2008G Jancsó Pharmacological modulation of the transient receptor potential vanilloid-1 (TRPV1) receptor function offers a promising means of producing pain relief at the level of the primary sensory neuron. In this issue of the BJP, the pharmacological approaches and the available experimental data that focus on the TRPV1 receptor to achieve therapeutically useful alleviation of pain and inflammation are reviewed. The potentials to inactivate TRPV1 receptor function by site- and modality-specific TRPV1 antagonists, uncompetitive TRPV1 blockers and drugs interfering with TRPV1 sensitization, are evaluated. A crucial issue of producing pain relief at the level of the nocisensor remains whether it can be achieved solely through inactivation of the TRPV1 receptor or TRPV1 agonist-induced defunctionalization of the whole primary afferent neuron is required. The accumulated evidence indicates that both pharmacological modulation of the intracellular trafficking of the TRPV1 receptor and defunctionalization of the nocisensors by TRPV1 agonists are promising novel approaches to tame the TRPV1 receptor. British Journal of Pharmacology (2008) 155, 1139,1141; doi:fn1; published online 10 November 2008 [source] PRECLINICAL STUDY: FULL ARTICLE: The dopamine D3 receptor partial agonist CJB090 and antagonist PG01037 decrease progressive ratio responding for methamphetamine in rats with extended-accessADDICTION BIOLOGY, Issue 3 2010Laura Orio ABSTRACT Previous work suggests a role for dopamine D3-like receptors in psychostimulant reinforcement. The development of new compounds acting selectively at dopamine D3 receptors has opened new possibilities to explore the role of these receptors in animal models of psychostimulant dependence. Here we investigated whether the dopamine D3 partial agonist CJB090 (1,10 mg/kg, i.v) and the D3 antagonist PG01037 (8,32 mg/kg, s.c.) modified methamphetamine (0.05 mg/kg/injection) intravenous self-administration under fixed- (FR) and progressive- (PR) ratio schedules in rats allowed limited (short access, ShA; 1-hour sessions 3 days/week) or extended access (long access, LgA; 6 hour sessions 6 days/week). Under a FR1 schedule, the highest dose of the D3 partial agonist CJB090 selectively reduced methamphetamine self-administration in LgA but not in ShA rats, whereas the full D3 antagonist PG01037 produced no effect in either group. Under a PR schedule of reinforcement, the D3 partial agonist CJB090 reduced the maximum number of responses performed (,breakpoint') for methamphetamine in LgA rats at the doses of 5 and 10 mg/kg, and also it produced a significant reduction in the ShA group at the highest dose. However, the D3 full antagonist PG01037 only reduced PR methamphetamine self-administration in LgA rats at the highest dose of 32 mg/kg with no effect in the ShA group. The results suggest that rats might be more sensitive to pharmacological modulation of dopamine D3 receptors following extended access to methamphetamine self-administration, opening the possibility that D3 receptors play a role in excessive methamphetamine intake. [source] Sympathetic control of short-term heart rate variability and its pharmacological modulationFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 4 2007Jean-Luc Elghozi Abstract The static relationship between heart rate (HR) and the activity of either vagal or sympathetic nerves is roughly linear within the physiological range of HR variations. The dynamic control of HR by autonomic nerves is characterized by a fixed time delay between the onset of changes in nerve activity and the onset of changes in HR. This delay is much longer for sympathetically than for vagally mediated changes in HR. In addition, the kinetics of the HR responses shows the properties of a low-pass filter with short (vagal) and long (sympathetic) time constants. These differences might be secondary to differences in nervous conduction times, width of synaptic cleft, kinetics of receptor activation and post-receptor events. Because of the accentuated low-pass filter characteristics of the HR response to sympathetic modulation, sympathetic influences are almost restricted to the very-low-frequency component of HR variability, but the chronotropic effects of vagal stimulation usually predominate over those of sympathetic stimulation in this frequency band. Oscillations in cardiac sympathetic nerve activity are not involved in respiratory sinus arrhythmia (high-frequency component) and make a minor contribution to HR oscillations of approximately 10-s period (low-frequency component of approximately 0.1 Hz), at least in the supine position. In the latter case, HR oscillations are derived mainly from a baroreflex, vagally mediated response to blood pressure Mayer waves. Beta-blockers and centrally acting sympathoinhibitory drugs share the ability to improve the baroreflex control of HR, possibly through vagal facilitation, which might be beneficial in several cardiovascular diseases. [source] Early genomics of learning and memory: a reviewGENES, BRAIN AND BEHAVIOR, Issue 3 2006S. Paratore The characterization of the molecular mechanisms whereby our brain codes, stores and retrieves memories remains a fundamental puzzle in neuroscience. Despite the knowledge that memory storage involves gene induction, the identification and characterization of the effector genes has remained elusive. The completion of the Human Genome Project and a variety of new technologies are revolutionizing the way these mechanisms can be explored. This review will examine how a genomic approach can be used to dissect and analyze the complex dynamic interactions involved in gene regulation during learning and memory. This innovative approach is providing information on a new class of genes associated with learning and memory in health and disease and is elucidating new molecular targets and pathways whose pharmacological modulation may allow new therapeutic approaches for improving cognition. [source] Anandamide enhances IL-10 production in activated microglia by targeting CB2 receptors: Roles of ERK1/2, JNK, and NF-,BGLIA, Issue 2 2010Fernando Correa Abstract The endocannabinoid system exhibits anti-inflammatory properties by regulating cytokine production. Anandamide (AEA) down-regulates proinflammatory cytokines in a viral model of multiple sclerosis (MS). However, little is known about the mechanisms by which AEA exerts these effects. Microglial cells are the main source of cytokines within the brain and the first barrier of defense against pathogens by acting as antigen presenting cells. IL-10 is a key physiological negative regulator of microglial activation. In this study we show that AEA enhances LPS/IFN,-induced IL-10 production in microglia by targeting CB2 receptors through the activation of ERK1/2 and JNK MAPKs. AEA also inhibits NF-,B activation by interfering with the phosphorylation of I,B,, which may result in an increase of IL-10 production. Moreover, endogenously produced IL-10 negatively regulates IL-12 and IL-23 cytokines, which in its turn modify the pattern of expression of transcription factorsinvolved in Th commitment of splenocytes. This suggeststhat by altering the cytokine network, AEA could indirectly modify the type of immune responses within the central nervous system (CNS). Accordingly, pharmacological modulation of AEA uptake and degradation might be a useful tool for treating neuroinflammatory diseases. © 2009 Wiley-Liss, Inc. [source] Role of aquaporins in endothelial water transportJOURNAL OF ANATOMY, Issue 5 2002A. S. Verkman The aquaporins (AQP) are a family of homologous water channels expressed in many epithelial and endothelial cell types involved in fluid transport. AQP1 protein is strongly expressed in most microvascular endothelia outside of the brain as well as in endothelial cells in cornea, intestinal lacteals, and other tissues. AQP4 is expressed in astroglial foot processes adjacent to endothelial cells in the central nervous system. Transgenic mice lacking aquaporins have been useful in defining their role in mammalian physiology. Mice lacking AQP1 manifest defective urinary concentrating ability, in part because of decreased water permeability in renal vasa recta microvessels. These mice also show a defect in dietary fat processing that may involve chylomicron absorption by intestinal lacteals. There is preliminary evidence that AQP1 might play a role in tumour angiogenesis and in renal microvessel structural adaptation. However AQP1 in most endothelial tissues does not appear to have a physiological function despite its role in osmotically driven water transport. For example mice lacking AQP1 have low alveolar capillary water permeability but unimpaired lung fluid absorption, as well as unimpaired saliva and tear secretion, aqueous fluid outflow, and pleural and peritoneal fluid transport. In the central nervous system mice lacking AQP4 are partially protected from brain oedema in water intoxication and ischaemic models of brain injury. Therefore although the role of aquaporins in epithelial fluid transport is in most cases well understood there remain many questions about the role of aquaporins in endothelial cell function. It is unclear why many leaky microvessels strongly express AQP1 without apparent functional significance. Improved understanding of aquaporin endothelial biology may lead to novel therapies for human disease, such as pharmacological modulation of tumour angiogenesis, renal fluid clearance and intestinal absorption. [source] Analysis of the vitamin D system in cutaneous squamous cell carcinomasJOURNAL OF CUTANEOUS PATHOLOGY, Issue 3 2004Jörg Reichrath Background:, Increasing evidence points at an important function of vitamin D metabolites for growth regulation in various tissues, and new vitamin D analogs are interesting candidates for the treatment of malignancies, including squamous cell carcinomas (SCC). Methods:, We have analyzed expression of vitamin D receptor (VDR), vitamin D-25-hydroxylase (25-OHase), 25-hydroxyvitamin D-1,-hydroxylase (1,-OHase), and 1,25-dihydroxyvitamin D-24-hydroxylase (24-OHase) in SCC. Results:, Intensity of VDR immunoreactivity was increased in SCCs as compared to normal human skin. VDR staining did not correlate with histological type or grading, nor with markers for proliferation, differentiation, or apoptotic cells. Incubation of SCC cell lines (SCL-1, SCL-2) with calcitriol resulted in a dose-dependent suppression of cell proliferation (approximately up to 30%) in vitro, as measured by a tetrazolium salt (WST-1)-based colorimetric assay. RNA levels for VDR, 25-OHase, 1,-OHase, and 24-OHase were significantly elevated in SCCs as compared to HS, as measured by real-time polymerase chain reaction. Conclusions:, Our findings demonstrate that modulation of VDR expression and local synthesis or metabolism of vitamin D metabolites may be of importance for growth regulation of SCCs. Additionally, SCCs represent potential targets for therapy with new vitamin D analogs that exert little calcemic side effects or for pharmacological modulation of calcitriol synthesis/metabolism in these tumors. [source] Pre-synaptic BK channels selectively control glutamate versus GABA release from cortical and hippocampal nerve terminalsJOURNAL OF NEUROCHEMISTRY, Issue 2 2010Maria Martire J. Neurochem. (2010) 115, 411,422. Abstract In the present study, by means of genetic, biochemical, morphological, and electrophysiological approaches, the role of large-conductance voltage- and Ca2+ -dependent K+ channels (BK channels) in the release of excitatory and non-excitatory neurotransmitters at hippocampal and non-hippocampal sites has been investigated. The results obtained show that the pharmacological modulation of pre-synaptic BK channels selectively regulates [3H]d -aspartate release from cortical and hippocampal rat synaptosomes, but it fails to influence the release of excitatory neurotransmitters from cerebellar nerve endings or that of [3H]GABA, [3H]Noradrenaline, or [3H]Dopamine from any of the brain regions investigated. Confocal immunofluorescence experiments in hippocampal or cerebrocortical nerve terminals revealed that the main pore-forming BK , subunit was more abundantly expressed in glutamatergic (vGLUT1+) versus GABAergic (GAD65-67+) nerve terminals. Double patch recordings in monosynaptically connected hippocampal neurons in culture confirmed a preferential control exerted by BK channels on glutamate over GABA release. Altogether, the present results highlight a high degree of specificity in the regulation of the release of various neurotransmitters from distinct brain regions by BK channels, supporting the concept that BK channel modulators can be used to selectively limit excessive excitatory amino acid release, a major pathogenetic mechanism in several neuropsychiatric disorders. [source] A novel inducible tyrosine kinase receptor to regulate signal transduction and neurite outgrowthJOURNAL OF NEUROSCIENCE RESEARCH, Issue 12 2009Ronald W. Alfa Abstract Nervous system growth factor gene delivery can promote axonal growth and prevent cell death in animal models of CNS trauma and neurodegenerative diseases. The ability to regulate growth factor expression or signaling pathways downstream from growth factor receptors remains a desirable goal for in vivo gene transfer. To achieve precise pharmacological modulation of neurotrophin activity, we have generated a chimeric trkA receptor (ItrkA) by fusing the entire intracellular domain of the trkA high-affinity NGF receptor to two intracellular, modified FK506 binding domains for the synthetic small molecule dimerization ligand AP20187. Rat PC12 cells were transduced with lentiviral vectors containing ItrkA and green fluorescent protein (GFP; via an internal ribosome entry site). Treatment of ItrkA-expressing PC12 cells with AP20187 induced neurite outgrowth and differentiation in a time- and dose-dependent fashion, with a half-maximal response at a concentration of 1 nM AP20187. Seventy percent of cells responded to AP20187 by day 3. Western blots demonstrated that AP20187 treatment resulted in phosphorylation of Erk1/2 and Akt in ItrkA-transduced PC12 cells but not in nontransduced, naďve cells. Phosphorylation levels were comparable to levels obtained with 50 ng/ml nerve growth factor (NGF). In addition, ItrkA lentiviral transduction of primary E15 dorsal root ganglion neurons significantly increased neurite growth three- to fourfold in the presence of AP20187 compared with control GFP transduced and naďve neurons. These results demonstrate that small ligand-induced dimerization of the intracellular domain of trkA can efficiently simulate the biological activity of NGF and provide a means to regulate intracellular neurotrophin receptor signaling. © 2009 Wiley-Liss, Inc. [source] Cluster analysis of BOLD fMRI time series in tumors to study the heterogeneity of hemodynamic response to treatmentMAGNETIC RESONANCE IN MEDICINE, Issue 6 2003Christine Baudelet Abstract BOLD-contrast functional MRI (fMRI) has been used to assess the evolution of tumor oxygenation and blood flow after treatment. The aim of this study was to evaluate K-means-based cluster analysis as a exploratory, data-driven method. The advantage of this approach is that it can be used to extract information without the need for prior knowledge concerning the hemodynamic response function. Two data sets were acquired to illustrate different types of BOLD fMRI response inside tumors: the first set following a respiratory challenge with carbogen, and the second after pharmacological modulation of tumor blood flow using flunarizine. To improve the efficiency of the clustering, a power density spectrum analysis was first used to isolate voxels for which signal changes did not originate from noise or linear drift. The technique presented here can be used to assess hemodynamic response to treatment, and especially to display areas of the tumor with heterogeneous responses. Magn Reson Med 49:985,990, 2003. © 2003 Wiley-Liss, Inc. [source] Matrix Metalloproteinase 2 in Reduced-Size Liver Transplantation: Beyond the MatrixAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2010S. Padrissa-Altés We studied the contribution of matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9) to the beneficial effects of preconditioning (PC) in reduced-size orthotopic liver transplantation (ROLT). We also examined the role of c-Jun N-terminal kinase (JNK) and whether it regulates MMP2 in these conditions. Animals were subjected to ROLT with or without PC and pharmacological modulation, and liver tissue samples were then analyzed. We found that MMP2, but notMMP9, is involved in the beneficial effects of PC in ROLT. MMP2 reduced hepatic injury and enhanced liver regeneration. Moreover, inhibition of MMP2 in PC reduced animal survival after transplantation. JNK inhibition in the PC group decreased hepatic injury and enhanced liver regeneration. Furthermore, JNK upregulated MMP2 in PC. In addition, we showed that Tissue inhibitors of matrix metalloproteinases 2 (TIMP2) was also upregulated in PC and that JNK modulation also altered its levels in ROLT and PC. Our results open up new possibilities for therapeutic treatments to reduce I/R injury and increase liver regeneration after ROLT, which are the main limitations in living-donor transplantation. [source] Upregulation of K2P5.1 potassium channels in multiple sclerosisANNALS OF NEUROLOGY, Issue 1 2010Stefan Bittner BSc Objective Activation of T cells critically depends on potassium channels. We here characterize the impact of K2P5.1 (KCNK5; TASK2), a member of the 2-pore domain family of potassium channels, on T-cell function and demonstrate its putative relevance in a T-cell,mediated autoimmune disorder, multiple sclerosis (MS). Methods Expression of K2P5.1 was investigated on RNA and protein level in different immune cells and in MS patients' biospecimens (peripheral blood mononuclear cells, cerebrospinal fluid cells, brain tissue specimen). Functional consequences of K2P5.1 expression were analyzed using pharmacological modulation, small interfering RNA (siRNA), overexpression, electrophysiological recordings, and computer modeling. Results Human T cells constitutively express K2P5.1. After T-cell activation, a significant and time-dependent upregulation of K2P5.1 channel expression was observed. Pharmacological blockade of K2P5.1 or knockdown with siRNA resulted in reduced T-cell functions, whereas overexpression of K2P5.1 had the opposite effect. Electrophysiological recordings of T cells clearly dissected K2P5.1-mediated effects from other potassium channels. The pathophysiological relevance of these findings was demonstrated by a significant K2P5.1 upregulation in CD4+ and CD8+ T cells in relapsing/remitting MS (RRMS) patients during acute relapses as well as higher levels on CD8+ T cells of clinically isolated syndrome, RRMS, and secondary progressive multiple sclerosis patients during clinically stable disease. T cells in the cerebrospinal fluid from MS patients exhibit significantly elevated K2P5.1 levels. Furthermore, K2P5.1-positive T cells can be found in inflammatory lesions in MS tissue specimens. Interpretation Selective targeting of K2P5.1 may hold therapeutic promise for MS and putatively other T-cell,mediated disorders. ANN NEUROL 2010;68:58,69 [source] Gene expression in actinic keratoses: pharmacological modulation by imiquimodBRITISH JOURNAL OF DERMATOLOGY, Issue 6 2004B. Lysa Summary Background, Actinic keratoses (AKs) are premalignant lesions that can progress into squamous cell carcinoma. Imiquimod, which belongs to the new class of immune-response modifiers, was recently shown to be effective in the treatment of AKs. The underlying mechanisms are not fully understood. Objectives, To study the expression of individual genes in uninvolved skin and AKs before therapy and to elucidate the way in which the expression of these genes is influenced by imiquimod therapy. Methods, We treated 13 patients with AK with imiquimod and compared gene expression before, during (five patients) and after (eight patients) therapy with that in uninvolved skin. We analysed genes coding for inflammatory cytokines or their receptors, adhesion molecules, anti-apoptotic proteins, p53 and toll-like receptors (TLRs) by reverse-transcriptase polymerase chain reaction. Results, Comparing uninvolved skin and untreated AK, we found significant differences in the expression of interleukin (IL)-6, hurpin, TLR7 and TLR8. During imiquimod therapy, we detected a further upregulation of interferon-,, IL-6, IL-10 receptor 1 and TLR7. In contrast, two anti-apoptotic genes, hurpin and HAX-1, were downregulated. We did not detect significant differences in gene expression for p53, tumour necrosis factor-, and ,- and ,-catenins. Clinically, the upregulated expression of the proinflammatory cytokines correlated with the local inflammation induced by imiquimod. Conclusions, Our results indicate that specific differences in gene expression are detectable between AK and uninvolved skin. Imiquimod influenced the expression of most genes analysed in this study. This work extends previous findings on the effects of imiquimod on gene regulation in AKs. [source] Expression and functional role of adenosine receptors in regulating inflammatory responses in human synoviocytesBRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2010K Varani Background and purpose:, Adenosine is an endogenous modulator, interacting with four G-protein coupled receptors (A1, A2A, A2B and A3) and acts as a potent inhibitor of inflammatory processes in several tissues. So far, the functional effects modulated by adenosine receptors on human synoviocytes have not been investigated in detail. We evaluated mRNA, the protein levels, the functional role of adenosine receptors and their pharmacological modulation in human synoviocytes. Experimental approach:, mRNA, Western blotting, saturation and competition binding experiments, cyclic AMP, p38 mitogen-activated protein kinases (MAPKs) and nuclear factor (NF)-,B activation, tumour necrosis factor , (TNF-,) and interleukin-8 (IL-8) release were assessed in human synoviocytes isolated from patients with osteoarthritis. Key results:, mRNA and protein for A1, A2A, A2B and A3 adenosine receptors are expressed in human synoviocytes. Standard adenosine agonists and antagonists showed affinity values in the nanomolar range and were coupled to stimulation or inhibition of adenylyl cyclase. Activation of A2A and A3 adenosine receptors inhibited p38 MAPK and NF-,B pathways, an effect abolished by selective adenosine antagonists. A2A and A3 receptor agonists decreased TNF-, and IL-8 production. The phosphoinositide 3-kinase or Gs pathways were involved in the functional responses of A3 or A2A adenosine receptors. Synoviocyte A1 and A2B adenosine receptors were not implicated in the inflammatory process whereas stimulation of A2A and A3 adenosine receptors was closely associated with a down-regulation of the inflammatory status. Conclusions and implications:, These results indicate that A2A and A3 adenosine receptors may represent a potential target in therapeutic modulation of joint inflammation. [source] Activation of the transient receptor potential vanilloid-1 (TRPV1) channel opens the gate for pain reliefBRITISH JOURNAL OF PHARMACOLOGY, Issue 8 2008G Jancsó Pharmacological modulation of the transient receptor potential vanilloid-1 (TRPV1) receptor function offers a promising means of producing pain relief at the level of the primary sensory neuron. In this issue of the BJP, the pharmacological approaches and the available experimental data that focus on the TRPV1 receptor to achieve therapeutically useful alleviation of pain and inflammation are reviewed. The potentials to inactivate TRPV1 receptor function by site- and modality-specific TRPV1 antagonists, uncompetitive TRPV1 blockers and drugs interfering with TRPV1 sensitization, are evaluated. A crucial issue of producing pain relief at the level of the nocisensor remains whether it can be achieved solely through inactivation of the TRPV1 receptor or TRPV1 agonist-induced defunctionalization of the whole primary afferent neuron is required. The accumulated evidence indicates that both pharmacological modulation of the intracellular trafficking of the TRPV1 receptor and defunctionalization of the nocisensors by TRPV1 agonists are promising novel approaches to tame the TRPV1 receptor. British Journal of Pharmacology (2008) 155, 1139,1141; doi:fn1; published online 10 November 2008 [source] The genetics of antiplatelet drug resistanceCLINICAL GENETICS, Issue 1 2009G Feher Platelets have a central role in the development of arterial thrombosis and subsequent cardiovascular events. An appreciation of this complex process has made antiplatelet therapy the cornerstone of cardiovascular disease management. However, numerous patients will experience a recurrent atherothrombotic vascular event despite adequate antiplatelet therapy. Individual differences in the rate of platelet activation and reactivity markedly influence normal hemostasis and the pathological outcome of thrombosis. Such an individual variability is largely determined by environmental and genetic factors. These are known to either hamper platelets' response to agonists, and thereby mimic the pharmacological modulation of platelet function or mask therapy effect and sensitize platelets. In this article, we reviewed the antiplatelet mechanisms of aspirin and clopidogrel and the possible role of different polymorphisms, which may affect the efficacy of antiplatelet therapy. Heterogeneity in the way patients respond to aspirin and clopidogrel may in part reflect variation in cyclooxygenase (COX)-1, COX-2, glycoprotein (GP) Ib alpha, GP Ia/IIa, GP IIb/IIIa, UGT1A6*2, P2Y1, P2Y12, CYP2C9, CYP3A4 and CYP3A5 genotypes. [source] Effects of pharmacological adrenergic and vagal modulation on fractal heart rate dynamicsCLINICAL PHYSIOLOGY AND FUNCTIONAL IMAGING, Issue 5 2001Mikko P. Tulppo Breakdown of short-term fractal-like behaviour of HR indicates an increased risk for adverse cardiovascular events and mortality, but the pathophysiological background for altered fractal HR dynamics is not known. Our aim was to study the effects of pharmacological modulation of autonomic function on fractal correlation properties of heart rate (HR) variability in healthy subjects. Short-term fractal scaling exponent (,1) along with spectral components of HR variability were analysed during the following pharmacological interventions in healthy subjects: (i) noradrenaline (NE) infusion (n=22), (ii) NE infusion after phentolamine (PHE) (n=8), (iii) combined NE + adrenaline (EPI) infusion (n=12), (iv) vagal blockade with high dose of atropine (n=10), (v) and vagal activation by low dose of atropine (n=10). Then ,1 decreased progressively during the incremental doses of NE (from 0·85 ± 0·250 to 0.55 ± 0·23, P<0·0001). NE also decreased the average HR (P<0·001) and increased the high frequency spectral power (P<0·001). Vagal blockade with atropine increased the ,1 value (from 0·82 ± 0·22 to 1·24 ± 0·41, P<0·05). Combined NE + EPI infusion and vagal activation with a low dose atropine did not result in any changes in ,1, and ,-adrenergic blockade by PHE did not completely reverse the effects of NE on ,1. Increased levels of circulating NE result in reduction of short-term correlation properties of HR dynamics. The results suggest that coactivation of cardiac vagal outflow at the time of high levels of a circulating sympathetic transmitter explains the breakdown of fractal-like behaviour of human HR dynamics. [source] | |||||||||||||||||||||||||