The Bezold-Jarisch Reflex and The Inflammatory Response Modulation in Unanesthetized Endotoxemic Rats

Evidence indicates that the activation of the parasympathetic branch of the autonomic nervous system may be effective in treating inflammatory diseases. Previously, we have described that baroreflex activation displays anti-inflammatory properties. Analogous to the baroreflex, the Bezold-Jarisch reflex also promotes parasympathetic activation with simultaneous inhibition of the sympathetic system. Thus, the present study aimed to evaluate whether the activation of the Bezold-Jarisch reflex would also have the ability to reduce inflammation in unanesthetized rats. We used lipopolysaccharide (LPS) injection (5mg/kg, i.p.) to induce systemic inflammation in male Wistar Hannover rats and phenylbiguanide (PBG) administration (5μg/kg, i.v.) to activate the Bezold-Jarisch reflex. Spleen, heart, hypothalamus, and blood samples were collected to determine the levels of cytokines. Compared to baseline, PBG reduced the arterial pressure (115±2 vs. 88±5mmHg) and heart rate (380±7 vs. 114±26bpm), immediately after its administration, confirming the activation of the parasympathetic system and inhibition of the sympathetic system. From the immunological point of view, the activation of the Bezold-Jarisch reflex decreased the plasma levels of TNF (LPS: 775±209 vs. PBG + LPS: 248±30pg/ml) and IL-6 levels in the spleen (LPS: 39±6 vs. PBG + LPS: 24±4pg/mg of tissue). However, it did not change the other cytokines in the plasma or the other tissues evaluated. These findings confirm that the activation of the Bezold-Jarisch reflex can modulate inflammation and support the understanding that the cardiovascular reflexes regulate the immune system.

522 Reduced sympatho-vagal responses to orthostatic stress in drug-naïve idiopathic restless legs syndrome

Introduction Restless legs syndrome (RLS) is a risk factor for cardiovascular disease (CVD). However, there are no electrophysiological biomarkers to assess this risk. This study aimed to evaluate the heart rate variability (HRV) and autonomic control of cardiovascular reflexes in the supine and standing positions in patients with RLS during wakefulness. Methods Fourteen drug-naïve RLS patients (12 women, 2 men; mean age: 42.14 ± 7.81 years) and 10 healthy controls underwent tests for blood pressure, heart rate when in the supine-rest and standing positions, deep breathing, and handgrip in controlled laboratory conditions. Five-minute R-R intervals in each position were collected and analyzed for HRV. Results Cardiovascular changes during deep breathing and isometric handgrip maneuvers were normal and similar between the two groups. The normalized unit of the low frequency component and low frequency/high frequency (LH/HF) ratio during standing were lower in the RLS patients than in the controls. LF/HF ratio responses during positional change from supine-rest to standing were significantly reduced in the RLS patients (RLS patients: mean ± SD, 2.94 ± 3.11; controls: 7.51 ± 5.58; P = 0.042). In Spearman’s rank correlation, ISI and PSQI were associated with HRV parameters. Conclusion The RLS patients showed reduced sympatho-vagal responses during positional change from supine-rest to standing during wakefulness, and RLS-related sleep disturbance was an important contributing factor for autonomic nervous system dysfunction. Reduced HRV responses during wakefulness might be a good predictor for CVD risk. Support (if any):

Synuclein Deficiency Results in Age-Related Respiratory and Cardiovascular Dysfunctions in Mice

Synuclein (α, β, and γ) proteins are highly expressed in presynaptic terminals, and significant data exist supporting their role in regulating neurotransmitter release. Targeting the gene encoding α-synuclein is the basis of many animal models of Parkinson’s disease (PD). However, the physiological role of this family of proteins in not well understood and could be especially relevant as interfering with accumulation of α-synuclein level has therapeutic potential in limiting PD progression. The long-term effects of their removal are unknown and given the complex pathophysiology of PD, could exacerbate other clinical features of the disease, for example dysautonomia. In the present study, we sought to characterize the autonomic phenotypes of mice lacking all synucleins (α, β, and γ; αβγ−/−) in order to better understand the role of synuclein-family proteins in autonomic function. We probed respiratory and cardiovascular reflexes in conscious and anesthetized, young (4 months) and aged (18–20 months) αβγ−/− male mice. Aged mice displayed impaired respiratory responses to both hypoxia and hypercapnia when breathing activities were recorded in conscious animals using whole-body plethysmography. These animals were also found to be hypertensive from conscious blood pressure recordings, to have reduced pressor baroreflex gain under anesthesia, and showed reduced termination of both pressor and depressor reflexes. The present data demonstrate the importance of synuclein in the normal function of respiratory and cardiovascular reflexes during aging.

DIAGNOSTIC POTENTIAL OF SELECTED SALIVARY PROTEOMICS FOR AUTONOMIC NERVOUS SYSTEM ACTIVITY ASSESSMENT

The clinical assessment of autonomic nervous system (ANS) functioning, enabling the diagnosis of autonomic neuropathy present in the course of many diseases, is currently based on performing simple cardiovascular reflexes (Ewing tests), analyzing heart rate variability (HRV) or heart rate turbulence (HRT), examining skin sweating or recording neurophysiological tests (e.g. microneurography). Laboratory assessment of ANS function is very scarce and practically only includes the plasma assessment of noradrenaline as a surrogate for the biochemical indicator of sympathetic activity. Recently, the possibility of evaluation of selected compounds present in saliva as laboratory markers of not only oral diseases but also systemic diseases has been raised. This work focuses on a brief description of the anatomy and physiology of the salivary glands and describes the formation of saliva, its composition and the use of this bodily fluid in laboratory diagnostics. In addition, the paper specifically discusses the possibility of determining selected compounds that are considered to reflect autonomic activity. A review of the literature indicates primarily four proteomics: two neuropeptides (vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY) that are co-transmitters in autonomic fibers, chromogranin A, a synaptic vesicle protein and α-amylase, a hydrolytic enzyme pre-digesting carbohydrates in the oral cavity. These are currently the most widely investigated agents for their usefulness as laboratory markers of ANS activity.