Alterations In Sympathetic Activity Research Articles

Autonomic dysfunction in posttraumatic stress disorder indexed by heart rate variability: a meta-analysis.

Changes in autonomic nervous system (ANS) function have been observed in a variety of psychological disorders, including posttraumatic stress disorder (PTSD). Analysis of heart rate variability (HRV) provides insight into the functioning of the ANS. Previous research on PTSD found lower HRV in PTSD patients compared to controls, indicating altered sympathetic and parasympathetic activity, but findings are inconsistent. The purpose of this meta-analysis was to examine differences in HRV indices between individuals with PTSD and healthy controls at baseline and during stress. The included primary studies present an aggregate of studies analyzing different HRV indices. Examined HRV indices were standard deviation of the normalized NN-intervals (SDNN), root mean square of successive differences (RMSSD), low-frequency (LF) and high-frequency (HF) spectral components, LF/HF ratio, and heart rate (HR). Moderating effects of study design, HRV and PTSD assessment, and sample characteristics were examined via subgroup-analyses and meta-regressions. Random-effects meta-analyses for HRV parameters at rest revealed significant group differences for RMSSD and HF-HRV, suggesting lower parasympathetic activity in PTSD. The aggregated effect size for SDNN was medium, suggesting diminished total variability in PTSD. A small effect was found for LF-HRV. A higher LF/HF ratio was found in the PTSD sample as compared to controls. Individuals with PTSD showed significantly higher HR. During stress, individuals with PTSD showed higher HR and lower HF-HRV, both indicated by small effect sizes. Findings suggest that PTSD is associated with ANS dysfunction.

Depression affects autonomic system of the body? Yes, it does!

BACKGROUND:Depression is a disorder of the brain, a state of low mood and aversion to activity that can affect a person's thoughts, behavior, feelings, and sense of well-being and can cause alteration in sympathetic activity of the body, thus affecting heart rate variability (HRV).AIM:The study was conducted to determine the effects of depression on HRV parameters in clinically known cases of depression.MATERIALS AND METHODS:A cross-sectional (observational) study was conducted on fifty known patients of depression, aged 18–65 years, and fifty healthy, age-matched, normal controls. HRV test was conducted, and the results were analyzed statistically using Student's “t”-test for equal variance, for various parameters.RESULTS:The study showed that the differences in mean R-R interval(s), mean HR (beats/min), very low frequency (VLF) power (milliseconds squared [ms2]), and low frequency/high frequency (LF/HF) power (%) (LF/HF ratio) among controls and cases were statistically highly significant, while the differences in LF power (ms2) in controls and cases were statistically significant. However, the differences in basic anthropometric parameters, STD (standard deviation of the normal to normal)(s), root mean square successive difference (ms), NN50 (count), pNN50 (%), VLF peak (Hz), LF peak (Hz), HF peak (Hz), HF power (ms2), VLF power (%), LF power (%), HF power (%), LF power (nu), and HF power (nu) were found to be statistically insignificant.CONCLUSION:Depression leads to changes in autonomic control of the body and changes the autonomic balance in favor of an increased sympathetic tone, which can be detected with fair accuracy with HRV analysis.

Arterial Stiffness Can Be Modulated by Pressure-Independent Mechanisms in Hypertension.

BackgroundEffects of short‐term interventions on large‐artery stiffness assessed by pulse wave velocity (PWV) have mainly been explained by concomitant changes in blood pressure (BP). However, lower body negative pressure, which increases sympathetic activity and has other hemodynamic effects, has a specific effect on PWV in healthy volunteers.Methods and ResultsWe examined effects of lower‐limb venous occlusion (LVO), a similar intervention to lower‐body negative pressure that reduces BP but increases sympathetic activity and device‐guided breathing (DGB), which reduces both BP and sympathetic activity, on PWV in patients with essential hypertension (n=70 after LVO, n=45 after DGB and LVO in random order). The short‐acting calcium channel antagonist nifedipine was used as a control for changes in BP. LVO produced a small but significant reduction in mean arterial pressure of 1.8 (95% CI 0.3–3.4) mm Hg. Despite this, aortic and carotid‐femoral PWV increased during LVO by 0.8 (0.2–1.4) m/s and 0.7 (0.3–1.05) m/s, respectively. DGB reduced PWV by 1.2 (0.9–1.4) m/s, to a greater extent than did nifedipine 10 mg (reduction of 0.7 [0.1–1.3] m/s, P<0.05 compared with reduction during DGB). This occurred despite a greater decrease in BP with nifedipine compared with DGB.ConclusionsArterial stiffness can be modulated independently of BP over the short term. The mechanism could involve alterations in sympathetic activity or other as yet uncharacterized effects of LVO and DGB.

Lavare Cycle Does Not Induce Pulsatility in CF-LVAD Patients

Purpose The Lavare cycle (LC) is a pre-programmed speed modulation algorithm (SMA) in the HeartWare continuous flow left ventricular assist device (HVAD) designed to increase ventricular and pump washout. We sought to determine whether the LC induced artificial pulsatility and alter sympathetic nervous system activity. Methods Ten HVAD patients were prospectively recruited. Patients were monitored for 24 hours using 3 devices and pulsatility metrics were calculated; 1) SphygmoCor 24-hour ambulatory oscillometric / tonometric blood pressure (BP) monitoring device was used to calculate pulse pressure (PP) and mean arterial pressure (MAP), 2) CDAS continuous pump data recorder was used to calculate a flow pulsatility index (PI), defined as (maximum - minimum flow)/(mean flow) and 3) Holter monitor (1000Hz) was used to calculate time domain measures of heart rate variability (HRV) to ascertain changes in sympathetic activity levels. Patients were monitored on two separate occasions, once with their LC on and once with it off. BP, flow and PI analyses were dichotomized for awake and asleep hours to account for diurnal variation in blood pressure and cardiac output. Results PP and MAP results were available for 9 patients, PI for 8 patients and HRV for 7 patients (table 1). There was no difference in PP, MAP or PI between the LC on and LC off groups. In terms of HRV, the LC on group had slightly higher heart rate (HR) compared to the LC off group (81.2 vs 78.7 bpm, p=0.028). There was no difference between groups in time domain measures of HRV (SDNN, standard deviation of normal-normal intervals; RMSSD root mean square of successive differences), markers of sympathetic and parasympathetic activity respectively. MAP was lower whilst asleep than awake (68.8 v 78.5, p=0.004), unaffected by LC. There were no differences between awake and asleep groups for PP, PI or mean flow (table 1). Conclusion LC is not associated with induced pulsatility or altered sympathetic activity in HVAD patients. MAP was lower in patients whilst asleep compared to when awake.

A7546 To study autonomic variability in offsprings of hypertensive parents in lucknow using handgrip dynamometer and galvanic skin response

Objectives: Positive family history of hypertension is one of the risk factors for being hypertensive in future life for children. Young adults with hypertensive first degree relatives constitute a special risk group that should be closely monitored. Early detection of proneness to hypertension may help an individual to lead a healthy life by altering his/her lifestyle. The aim of the present study is to investigate the autonomic variability in offspring of hypertensive parents. Methods: This is a case control study. In this study 60 healthy young subjects, (n = 60; 30 cases, 30 controls, age: 18–25 years both male and female) were chosen. The blood pressure of the participants was recorded using a electronic blood pressure instrument (Cannon). The participant was asked to sustain isometric handgrip at one third of Maximum voluntary contraction(MVC). At the completion of one minute, blood pressure was measured. Three minutes after the handgrip test, the blood pressure was noted again (recovery). GSR was recorded using Medicaid Polyrite machine. Results: In cases the diastolic blood pressure after 3 minutes of withdrawal of stressor was seen to be significantly higher (p value < 0.05) than baseline diastolic blood pressure. GSR recording was found to be significantly lower in cases than in controls (p value < 0.05). The change in skin potential is in response to stress which alters sympathetic activity. Conclusion: Once stimulated by a stressor, sympathetic system causes rise in blood pressure. The persons who show higher cardiovascular reactivity to a stressor but slower rate of recovery after the withdrawal of the stressor indicate that their autonomic control system is weak. Decreased GSR recordings also demonstrate altered sympathetic activity.

Mast cells modulate the pathogenesis of leptin-induced left stellate ganglion activation in canines

BackgroundLeptin is an adipocytokine predominantly secreted by adipose tissue that participates in immune modulation. Mast cells are important immune cells that are related to altered sympathetic activity. Previous study has shown that leptin promotes activation of the left stellate ganglion (LSG) directly via the leptin receptor. This study aims to investigate whether mast cells play a key role in indirect activation. MethodsTwenty-eight canines were randomly divided into 3 groups: the control group (saline, n = 8), leptin group (leptin, n = 9), and DSCG group (disodium cromoglycate plus leptin, n = 11). Drugs were locally microinjected into the LSG. The function and neural activity of the LSG were evaluated to investigate LSG activation. Tryptase was adopted to identify activated mast cells in the LSG. ResultsCompared with the control group, leptin injection (18 μg) markedly increased the function and neural activity of the LSG. Leptin also upregulated c-fos, nerve growth factor (NGF), and tryptase expression in the LSG. However, these effects of leptin were attenuated by pre-injection of DSCG (25 mg). Additionally, the immunofluorescence analysis revealed that many mast cells were present in the LSG and that those cells were located close to sympathetic neurons. The presence of leptin receptors on the mast cells was verified. ConclusionsImmune mast cells play an important supplementary role in the pathogenesis of leptin-induced LSG activation.

Synergistical action of the β2 adrenoceptor and fatty acid binding protein 2 polymorphisms on the loss of glomerular filtration rate in Chinese patients with type 2 diabetic nephropathy.

Since altered sympathetic nerve activity and insulin resistance are implicated in the pathogenesis of type 2 diabetic nephropathy, we investigated the effect of polymorphic Arg16Gly and Gln27Glu in the β2 adrenoceptor gene and Ala54Thr in the fatty acid binding protein 2 gene on the estimated glomerular filtration rate (eGFR) in Chinese patients with the above disease. A total of 552 diabetic subjects recruited from annual health examinations were studied. The eGFR was calculated from the Modification of Diet in Renal Disease equation for the Chinese. Plasma norepinephrine level and genotype were determined by high-performance liquid chromatography-tandem mass spectrometry and TaqMan method, respectively. Holter-derived heart rate viability (HRV) and the MRI-generated renal apparent diffusion coefficient (ADC) were evaluated. The Gly16Gly and Thr54Thr homozygotes had significantly higher microalbuminuria and lower eGFR against other genotypes in their individual polymorphism. Besides, the Gly16Gly variant exhibited markedly elevated norepinephrine level, whereas indicative of insulin resistance was increased in the Thr54Thr one. Multiple linear regression analysis further confirmed the independent genetic effect on the eGFR. Moreover, multifactor dimensionality reduction method detected a gene-gene synergistic action that subjects with the Gly16Gly/Thr54Thr genotype were exposed to higher risk of eGFR loss. Finally, these findings were accompanied by lower HRV and ADC, indicating sympathetically mediated hemodynamic changes. By uncovering the genetic component of the coherent interplay between the elevated sympathetic nerve activity and metabolic disorders, our observations might promote the development of novel personalized prevention and management strategies against the diabetic nephropathy, especially in the genetically susceptible individuals.

Unintended Consequences: Renal Denervation Attenuates Hypertension Development but Impairs Glucose Metabolism in Female Fawn‐Hooded Hypertensive Rats

For both men and women, hypertension (HTN) is the highest risk factor for cardiovascular disease and stroke – the two leading causes of morbidity and mortality throughout the world. Though HTN etiology remains debated, altered sympathetic nervous activity, particularly to the kidney (RSNA), is regarded as a primary contributor to the development and maintenance of HTN. Ablation of renal sympathetic nerves (RDNx) reportedly prevents and/or reverses several forms of experimental hypertension. Several off‐target improvements are also reported, such as glucose metabolism. However, an overwhelming majority of these experimental models and mechanisms focus only on responses in male subjects. Moreover, the sex differences in sympathetic control of blood pressure in hypertension remain poorly defined. In this study, we assessed the role of RDNx to prevent hypertension development and metabolic dysfunction in the Fawn‐Hooded Hypertensive (FHH) rat model. We hypothesized that RDNx would attenuate the development of HTN, and improve glucose handling in female and male rats. FHH rats (10 weeks old) underwent sham or bilateral RDNx surgeries (n=5/group). For the following six weeks, 24‐hour mean arterial pressure (MAP) was monitored by radiotelemetry. Glucose handling was assessed biweekly by glucose tolerance test (GTT). Cardiovascular data was averaged weekly, and analyzed by two‐way ANOVA with a Bonferroni post‐hoc test (α=.05). Data presented as mean ± SEM. Six weeks post‐treatment, RDNx attenuated the HTN in the females (p&lt;.05) vs. sham controls (107±5 vs. 118±3). Interestingly, no difference in MAP between RDNx and sham males was observed (129±2 vs. 125±1mmHg). Regarding glucose metabolism, baseline fasting blood glucose (FBG) and glucose tolerance (GT) were similar between males and females prior to RDNx. After six weeks, FBG in female sham FHH (100.9±2.3mg/dL) was higher (p&lt;.05) than male shams (89.2±2.7mg/dL). Likewise, GT was impaired in female rats compared to male shams. In contrast to our hypothesis, RDNx worsened the FBG (110±2.6mg/dL) and GT in female vs. female shams. No effect of time or RDNx on glucose handling was observed males. In summary, RDNx attenuated HTN development in female FHH rats; however, glucose metabolism was impaired by RDNx in females but not in males. These results suggest that sex may need to be considered in the use of RDNx to treat HTN. These findings are clinically important in that RDNx responses may be partially dependent on sex, and may result in negative outcomes such as impaired glucose metabolism in females. Further examination of sex differences in the responses to RDNx is underway.Support or Funding InformationNIH 5R01HL116476; NIH 2T32HL7741

The baroreflex as a long-term controller of arterial pressure.

Because of resetting, a role for baroreflexes in long-term control of arterial pressure has been commonly dismissed in the past. However, in recent years, this perspective has changed. Novel approaches for determining chronic neurohormonal and cardiovascular responses to natural variations in baroreceptor activity and to electrical stimulation of the carotid baroreflex indicate incomplete resetting and sustained responses that lead to long-term alterations in sympathetic activity and arterial pressure.

Chronic thoracic spinal cord injury impairs CD8+ T-cell function by up-regulating programmed cell death-1 expression

BackgroundChronic spinal cord injury (SCI) induces immune depression in patients, which contributes to their higher risk of developing infections. While defects in humoral immunity have been reported, complications in T-cell immunity during the chronic phase of SCI have not yet been explored.MethodsTo assess the impact of chronic SCI on peripheral T-cell number and function we used a mouse model of severe spinal cord contusion at thoracic level T9 and performed flow cytometry analysis on the spleen for T-cell markers along with intracellular cytokine staining. Furthermore we identified alterations in sympathetic activity in the spleen of chronic SCI mice by measuring splenic levels of tyrosine hydroxylase (TH) and norepinephrine (NE). To gain insight into the neurogenic mechanism leading to T-cell dysfunction we performed in vitro NE stimulation of T-cells followed by flow cytometry analysis for T-cell exhaustion marker.ResultsChronic SCI impaired both CD4+ and CD8+ T-cell cytokine production. The observed T-cell dysfunction correlated with increased expression of programmed cell death 1 (PD-1) exhaustion marker on these cells. Blocking PD-1 signaling in vitro restored the CD8+ T-cell functional defect. In addition, we showed that chronic SCI mice had higher levels of splenic NE, which contributed to the T-cell exhaustion phenotype, as PD-1 expression on both CD4+ and CD8+ T-cells was up-regulated following sustained exposure to NE in vitro.ConclusionsThese studies indicate that alteration of sympathetic activity following chronic SCI induces CD8+ T-cell exhaustion, which in turn impairs T-cell function and contributes to immune depression. Inhibition of the exhaustion pathway should be considered as a new therapeutic strategy for chronic SCI-induced immune depression.

Improvements in Left Ventricular Hypertrophy and Diastolic Function Following Renal Denervation: Effects Beyond Blood Pressure and Heart Rate Reduction

This study sought to investigate the interaction between blood pressure (BP) and heart rate (HR) reduction and changes in left ventricular (LV) structure and function following renal sympathetic denervation (RDN). Hypertension results in structural and functional cardiac changes. RDN reduces BP, HR, and LV mass and improves diastolic dysfunction. We evaluated LV size, mass, and function before and 6 months after RDN in 66 patients with resistant hypertension and analyzed results in relation to systolic BP (SBP) and HR. SBP decreased by 11 ± 3 mm Hg in the first, 18 ± 5 mm Hg in the second, and 36 ± 7 mm Hg in the third tertile of SBP at baseline (p < 0.001). HR decreased by 13 ± 4 beats/min, 8 ± 3 beats/min, and 11 ± 6 beats/min in tertiles of SBP (p for interaction between tertiles = 0.314). In all SBP tertiles, LV mass index (LVMI) decreased similarly (LVMI −6.3 ± 2.2 g/m 2.7 , −8.3 ± 2.1 g/m 2.7 , and −9.6 ± 1.9 g/m 2.7 ; p for interaction = 0.639). LVMI decreased unrelated to HR at baseline (p for interaction = 0.471). The diastolic parameters E-wave deceleration time, isovolumetric relaxation time, and E′-wave velocity improved similarly in all tertiles of SBP and HR. Changes in LV mass and function were also unrelated to reduction in SBP or HR. Vascular compliance improved dependently on BP but independently of HR reduction. In patients with resistant hypertension, LV hypertrophy and diastolic function improved 6 months after RDN, without significant relation to SBP and HR. These findings suggest a direct effect of altered sympathetic activity in addition to unloading on cardiac hypertrophy and function.

The carotid body in cardiovascular disease: more chicken and egg than horse and cart?

The carotid body in cardiovascular disease: more chicken and egg than horse and cart?

Assessment of Cold Induced Alterations in Catecholamine Turnover of Lean and Glutamate-treated Obese Rats

Excretion of norepinephrine (NE) and vanillylmandelic acid (VMA) in urine as well as NE-turnover in tissues from lean and glutamate-treated obese rats were determined in warm and cold environment. NE-and VMA-excretion in urine was elevated by cold exposure, indicating an activation of the sympathetic nervous system in animals of both groups. Organspecific NE-turnover responds with higher sensitivity to cold in obese rats but without complete compensation in brown adipose tissue. Urinary NE- and VMA- excretion as well as NE-turnover in organs confirmed that cold exposure activates the sympathetic nervous system. Measurement of NE-turnover in tissues gives organspecific information regarding alterations in sympathetic activity during cold exposure, whereas excretion of NE and VMA in urine is a summarizing measure for the whole body turnover only.

Catecholamine alterations in pediatric obstructive sleep apnea: Effect of obesity

Obstructive sleep apnea (OSA) elicits increased sympathetic activity in adults and increased urinary catecholamines. Moreover, urinary catecholamine excretion is altered in obese patients. We hypothesized that morning urine catecholamine levels would be correlated with the severity of obstructive sleep apnea and degree of obesity in children. Children referred to the pediatric sleep center for habitual snoring underwent overnight polysomnography, and the first morning voided urine sample was collected. Urinary concentrations of norepinephrine, epinephrine and dopamine were measured and corrected for creatinine levels. In a subset of children, blood samples were drawn and gene expression of catecholamine-relevant genes analyzed by quantitative real-time PCR. One hundred fifty-nine children were recruited and completed the protocol. Children with OSA had significantly higher urinary norepinephrine and epinephrine levels, but not dopamine, compared to habitual snorers (norepinephrine: 40.1 +/- 24.7 ng/mg creatinine vs. 31.6 +/- 16.2 ng/mg creatinine, P < 0.01; epinephrine: 6.4 +/- 10.5 ng/mg vs. 4.5 +/- 0.5 ng/mg, P < 0.01). There was a positive correlation between norepinephrine and epinephrine values and polysomnographic indices, but no effect of obesity on catecholamine levels. In addition, expression of several of the major genes involved in synthesis and transport of catecholamines, as well as in selected receptors were compatible with increased bioavailability of catecholamines. In children with OSA, morning urinary norepinephrine and epinephrine levels are significantly higher than those without OSA, and correlate with the severity of the disease. Gene expression patterns are in agreement with such findings. Urine catecholamine levels do not appear to be influenced by the presence of obesity. Thus, altered sympathetic activity in OSA patients appears to occur independently of the presence of obesity.

Neuronal Regulators and Vascular Dysfunction in Raynauds Phenomenon and Systemic Sclerosis

Raynaud's phenomenon (RP) results from an exaggerated cutaneous vasospastic response to cold or emotional stress. The mechanisms that lead to impaired cutaneous vascular tone are complex. The regulation of cutaneous vasoconstriction and vasodilation, involves altered sympathetic nerve activity and a host of neuronal regulators, including adrenergic and non-adrenergic, as well as REDOX signalling and other signalling such as the RhoA/ROCK pathway. This review summarises the literature concerning the regulation of vascular tone by neurohumoral factors that may be involved in RP and systemic sclerosis (SSc).

Trigeminal trophic syndrome with extensive ulceration following herpes zoster

The trigeminal trophic syndrome is a rare complication following central or peripheral injury of the trigeminal nerve typically characterized by unilateral distribution of anaesthesia, paraesthesia and ulceration. In one third of cases it is preceded by an iatrogenic damage of the trigeminal nerve, in another third by a history of stroke. Other causes include head trauma, intracranial tumours, herpes virus infection, degenerative diseases of the CNS and idiopathic. Little is known about the pathogenesis. Contribution of neurotrophic factors and an altered sympathetic activity is assumed but a pivotal role of self-mutilation is generally accepted. We report a case of a patient who developed a strictly unilateral crescent ulcer of the ala nasi in addition to an extensive ulceration of the forehead and scalp following herpes zoster ophthalmicus.

Sympathetic nervous modulation of the skin innate and adaptive immune response to peptidoglycan but not lipopolysaccharide: Involvement of β-adrenoceptors and relevance in inflammatory diseases

Disorders of the skin immune activity are implicated in the pathogenesis of acquired inflammatory skin disorders. Inflammatory diseases including psoriasis, atopic dermatitis, lichen planus and vitiligo have also been associated with local alterations of adrenergic mechanisms and emotional stress. Here we show that the β-adrenergic receptors antagonist propranolol along with peptidoglycan, but not LPS, combined with intradermal injection of a soluble protein, shifted the recall memory response to the Th1 type. The specific β2-AR antagonist ICI 118,551 did not reproduce this effect suggesting that inhibition of both β1- and β2-AR caused the Th1 polarization. The underlying mechanism included enhanced local expression of IFN-γ, IL-12 and IL-23 as well as of IFN-β and CXCR3 ligands during the innate phase of the response which resulted in an increase of antigen-positive plasmacytoid dendritic cells (pDCs) in the draining lymph node. In particular, modulation of inflammatory cytokines, and IFN-β inducible genes expression appeared to involve also the β1-AR. Plasmacytoid dendritic cells and IL-23 were recently reported to play a central role in the pathogenesis of Th1-sustained inflammatory skin diseases such as psoriasis. Thus, primary β-adrenoceptors signaling defects or altered sympathetic nervous activity together with selected pattern recognition receptors activation might serve as initiation and/or persistence factors for numerous Th1-sustained inflammatory skin diseases.

Essential hypertension seems to result from melatonin-induced epigenetic modifications in area postrema

Essential hypertension is a complex multifactorial disorder with epigenetic and environmental factors contributing to its prevalence. Epigenetic system is a genetic regulatory mechanism that allows humans to maintain extraordinarily stable patterns of gene expression over many generations. Sympathetic nervous system plays a major role in the maintenance of hypertension and the rostral ventrolateral medulla is the main source of this sympathetic activation. A possible mechanism to explain the sympathetic hyperactivity in the rostral ventrolateral medulla is an action of the area postrema. Area postrema seems to be the region where a shift of the set-point to a higher operating pressure occurs resulting in hypertension. But, how can a shift occur in the area postrema. We propose that melatonin-induced epigenetic modifications in the neurons of area postrema plays a role in this shift. Area postrema is reported to contain high levels of melatonin receptors that play a role in the epigenetic modifications in certain cells. Environmental stressors cause epigenetic modifications in the neurons of area postrema via the pineal hormone melatonin and these changes lead to a shift in the set-point to a higher operating pressure. This signal is then sent via efferent projections to key medullary sympathetic nuclei in rostral ventrolateral medulla resulting in increases in sympathetic nerve activity. This model may explain the long-term alterations in sympathetic activity in essential hypertension.

Simultaneous measurement of parasympathetic reflex vasodilator and arterial blood pressure responses in the cat

We measured the changes in lower lip blood flow and systemic arterial blood pressure evoked by lingual nerve or trigeminal spinal nucleus (Vsp) stimulation to gain an insight into the brainstem integration of sympathetic and parasympathetic responses to nociceptive stimulation. We used artificially ventilated, cervically vago-sympathectomized cats deeply anesthetized with α-chloralose and urethane. A lip blood flow increase occurred in an intensity- and frequency-dependent manner following electrical stimulation of Vsp or lingual nerve regardless of whether systemic arterial blood pressure increased or decreased. In contrast, there was no apparent optimal frequency for the changes in systemic arterial blood pressure elicited by electrical stimulation of Vsp or lingual nerve. No relationship was found between the amplitude of the lip blood flow increase and that of the systemic arterial blood pressure change. Microinjection of lidocaine or kainic acid into the Vsp evoked, respectively, reversible and irreversible inhibition of the lip blood flow increase and systemic arterial blood pressure change evoked by lingual nerve stimulation. When microinjected unilaterally directly into the ipsilateral Vsp, the GABA agonist muscimol abolished both lingual nerve-evoked effects (increase in lip blood flow and changes in systemic arterial blood pressure) without changing basal systemic arterial blood pressure, suggesting the presence in the Vsp of GABA receptors serving to modulate both the parasympathetically mediated lip blood flow increase and the sympathetically mediated systemic arterial blood pressure change. Lidocaine microinjection into the salivatory nucleus caused a significant attenuation of the lingual nerve-induced blood flow increase, but had no effect on the lingual nerve-induced systemic arterial blood pressure change. Thus, the neural pathway mediating the lingual nerve-induced lip blood flow increase seems to be simple, requiring a minimum of four neurons: trigeminal afferent–Vsp–parasympathetic pre-ganglionic neurons with cell body located in the inferior salivatory nucleus–otic postganglionic neuron. On the other hand, the pathway underlying the evoked systemic arterial blood pressure changes, presumably mediated via altered sympathetic activity, seems to be more complicated and could be affected by more numerous factors.

Neuropeptide Y Receptors. Future Therapeutic Target in Congestive Heart Failure.

Peptides are known to be widely distributed in the body, particularly in the gut and the nervous system. In 1982, the presence of a novel brain peptide, neuropeptide Y (NPY) was reported. Subsequently, it was established that NPY is colocalized and co-released with norepinephrine and is distributed in both the central and the peripheral nervous systems. Other reports have indicated the possible role of NPY as a neuromodulator for the catecholaminergic neurons. Since altered sympathetic activity plays a crucial role in the pathophysiology of congestive heart failure, we examined the role of NPY in the modulation of sympathetic activity in various cardiovascular diseases including congestive heart failure. This review article will provide an insight into the status of the NPY receptor the possible therapeutic targets in congestive heart failure.