Increases in plasma neuropeptide Y concentrations during sympathetic activation in man

doi:10.1016/0165-1838(86)90089-5

Journal of the Autonomic Nervous System

Volume 17, Issue 2, October 1986, Pages 143-149

Journal of the Auton...

https://doi.org/10.1016/0165-1838(86)90089-5 Get rights and content

Abstract

Neuropeptide Y (NPY) coexists with noradrenaline in postganglionic sympathetic neurons. In order to test the hypothesis that NPY may be released along with catecholamines by activation of the sympathoadrenal system we measured plasma NPY-like immunoreactivity (NPY-LI) concentrations during cold pressor test, head up tilt and bicycle exercise in healthy volunteers. All 3 manoeuvres resulted in elevation of blood pressure, heart rate and plasma noradrenaline and adrenaline concentrations. These were accompanied by increases in plasma NPY-LI concentrations on cold pressor test and exercise, but not with head up tilt. The increases in both NPY-LI and catecholamines were greatest with exercise. These findings suggest that NPY is released at the same time as noradrenaline when sympathetic noradrenergic nerves are activated.

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Measured levels of catecholamines reflect metabolism and clearance, as well as resting sympathetic tone or release, and are affected by numerous confounding factors (including medications, diurnal variation and concomitant diseases) that can make interpretation difficult [37,38]. Other blood biomarkers of sympathetic activity (e.g., neuropeptide Y) have similar limitations [30,41]. Norepinephrine spillover studies, unlike plasma or urinary measurement, can assess organ-specific sympathetic activity but are invasive, expensive and technically challenging [37,38].
Rheumatoid arthritis (RA) is a chronic inflammatory condition with increased all-cause and cardiovascular mortality. Accumulating evidence indicates that the immune and autonomic nervous systems (ANS) are major contributors to the pathogenesis of cardiovascular disease. We performed the first systematic literature review to determine the prevalence and nature of ANS dysfunction in RA and whether there is a causal relationship between inflammation and ANS function.
Electronic databases (MEDLINE, Central and Cochrane Library) were searched for studies of RA patients where autonomic function was assessed.
A total of 40 studies were included. ANS function was assessed by clinical cardiovascular reflex tests (CCTs) (n = 18), heart rate variability (HRV) (n = 15), catecholamines (n = 5), biomarkers of sympathetic activity (n = 5), sympathetic skin responses (n = 5), cardiac baroreflex sensitivity (cBRS) (n = 2) and pupillary light reflexes (n = 2). A prevalence of ~60% (median, range: 20–86%) of ANS dysfunction (defined by abnormal CCTs) in RA was reported in 9 small studies. Overall, 73% of studies (n = 27/37) reported at least one of the following abnormalities in ANS function: parasympathetic dysfunction (n = 20/26, 77%), sympathetic dysfunction (n = 16/30, 53%) or reduced cBRS (n = 1/2, 50%). An association between increased inflammation and ANS dysfunction was found (n = 7/19, 37%), although causal relationships could not be elucidated from the studies available to date.
ANS dysfunction is prevalent in ~60% of RA patients. The main pattern of dysfunction is impairment of cardiovascular reflexes and altered HRV, indicative of reduced cardiac parasympathetic (strong evidence) activity and elevated cardiac sympathetic activity (limited evidence). The literature to date is underpowered to determine causal relationships between inflammation and ANS dysfunction in RA.
Comparison of the effects of pantethine and fursultiamine on plasma levels of adrenocorticotropic hormone and neuropeptide Y under continual stress exposure
2012, Biomedicine and Aging Pathology
Some abnormalities of gastrointestinal function are presumed to result from changes in levels of stress-related hormones from the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS), represented by adrenocorticotropic hormone (ACTH) and neuropeptide Y (NPY), respectively. We examined the effects of pantethine and fursultiamine on plasma levels of ACTH- and NPY-like immunoreactive substances (IS) in healthy subjects under continual stress from repetitive blood sampling. An open-labelled crossover study was conducted on five healthy volunteers. Each subject was administered a single oral dose each of pantethine, fursultiamine and placebo at intervals of one month. Venous blood samples were collected before and at 20, 40, 60, 90, 120, 180 and 240 minutes after each administration. Plasma levels of ACTH- and NPY-IS were measured using a highly sensitive enzyme immunoassay. Serial blood sampling increased plasma ACTH-IS and NPY-IS levels, presumably due to stress. Oral administration of pantethine resulted in a significant decrease in plasma ACTH-IS level compared to placebo. Fursultiamine administration resulted in a significant decrease in plasma NPY-IS level compared to placebo. These findings suggest that pantethine and fursultiamine may have modulatory effects on the HPA axis and SNS, respectively, and may be useful to treat postoperative ileus not only by improving gastrointestinal motility but also by ameliorating mental stress.
Mirtazapine suppresses the increases in plasma levels of adrenocorticotropic hormone and neuropeptide y under continual stress exposure
2012, Biomedicine and Aging Pathology
Citation Excerpt :
NPY is widely distributed in central and peripheral neurons [26–28], and is a sympathetic neurotransmitter and neuromodulator intricately involved in stress response of the body [29]. Since noradrenaline is rapidly oxidized, the more stable NPY is often used as an indicator of SNS activity in response to stressors [30]. Venipuncture for blood sampling has been proposed to be a stress factor that increases circulating ACTH and NPY levels [31,32].
Some depressions are presumed to result from changes in levels of stress-related hormones released from the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS), represented by adrenocorticotropic hormone (ACTH) and neuropeptide Y (NPY), respectively. Venipuncture for blood sampling has been proposed to be a stress factor that increases circulating ACTH and NPY levels. We examined the effects of mirtazapine on plasma levels of ACTH- and NPY-like immunoreactive substances (IS) in healthy subjects under continual stress induced by repetitive venipunctures for blood sampling. An open-labeled crossover study was conducted on eight healthy volunteers. Each subject was administered a single oral dose of mirtazapine or placebo at an interval of 1 month. Venous blood samples were collected repetitively before and after each administration. Plasma levels of ACTH- and NPY-IS were measured using a highly sensitive enzyme immunoassay. In the placebo group, plasma ACTH-IS levels at 240 min and NPY-IS levels at 40 min increased significantly compared with the levels before administration, presumably due to stress. Oral administration of mirtazapine resulted in significant decreases in plasma ACTH-IS level at 60 and 240 min and NPY-IS level at 20 and 40 min compared with placebo administration. These findings suggest that the antidepressant activity of mirtazapine may involve the suppression of not only the HPA axis but also the SNS.
Neuropeptide Y, an orexigenic hormone, regulates phagocytic activity of lizard splenic phagocytes
2011, Peptides
Present in vitro study in the wall lizard Hemidactylus flaviviridis, for the first time in ectothermic vertebrates, demonstrated the immunoregulatory role of neuropeptide Y (NPY) and its receptor-coupled downstream signaling cascade. NPY inhibited the percentage phagocytosis and phagocytic index of splenic phagocytes. The inhibitory effect of NPY on phagocytosis was completely antagonized by Y₂ and Y₅ receptor antagonists. This suggests that NPY mediated its effect on phagocytosis through Y₂ and Y₅ receptors. Further, NPY receptor-coupled downstream signaling cascade for NPY effect on phagocytosis was explored using the inhibitors of adenylate cyclase (SQ 22536) and protein kinase A (H-89). The SQ 22536/H-89 in a concentration-related manner decreased the inhibitory effect of NPY on phagocytosis. Further, an increase in intracellular cAMP level was observed in response to NPY. Taken together, it can be concluded that NPY via Y₂ and Y₅ receptor-coupled AC–cAMP–PKA pathway downregulated the phagocytic activity of lizard splenic phagocytes.
Hypothetical hormonal mechanism by which potassium-rich diets benefit patients with rheumatoid arthritis
2009, Medical Hypotheses
Patients with rheumatoid arthritis (RA) have significantly lower salivary and serum potassium (K) concentration, reduced total body K, and lower dietary K intake than healthy subjects. There may also be a subtle impairment in the hypothalamic–pituitary–adrenal (HPA) axis in patients with RA with both a poor cortisol secretion response as well as a lower adrenocorticotropin hormone (ACTH) response in relation to involved inflammatory factors. Patients with RA also exhibit an impaired Na+, K+-ATPase (NKA) activity which might promote the pro-inflammatory cytokine secretion seen in RA. I will use these facts to support the mechanism I propose.
There are no qualitative differences between the effects of endogenous cortisol and exogenously applied synthetic glucocorticoids (GCs), which are widely used to treat RA. All effects are transmitted via the same receptor. The GC, cortisol, plays a role in normal K homeostasis and the reverse is also seen with higher K intake leading to higher cortisol secretion and biosynthesis.
Results of a recent clinical trial showed elevated serum cortisol followed K supplementation. I suggest that this is what alleviated RA symptoms. I would like to suggest a “Cortisol-K” theory as a mechanism for De Coti-Marsh’s proposed “K theory” while not precluding the possibility of eventual proof of a cure, possibly from effects of K inside cells other than the adrenal glands.
Long-term cigarette smoke exposure increases uncoupling protein expression but reduces energy intake
2008, Brain Research
Citation Excerpt :
BAT and RpWAT were snap frozen in liquid nitrogen and stored at − 80 °C for later measurement of mRNA expression of UCP1, UCP3, TNFα, IL-6, and ATGL. As previously described (Morris et al., 1986) endogenous NPY from the various brain regions was extracted by boiling in 0.5 M acetic acid, and measured by the radioimmunoassay developed in our laboratory using synthetic NPY as standard (10–1280 pg/tube, Auspep, Australia). Plasma leptin, insulin and corticosterone concentrations were measured using commercially available radioimmunoassay kits (Linco, Missouri, USA; MP Biomedicals, Irvine, USA).
The appetite suppressing effect of tobacco is a major driver of smoking behaviour; however few studies have addressed the effects of chronic cigarette smoke exposure (SE) on appetite, body weight and metabolic markers. We compared the effects of SE to equivalent food restriction (pair-fed, PF), against sham-exposure, on body weight, adiposity, cytokines, and levels of uncoupling proteins (UCP) and brain neuropeptide Y (NPY) in male Balb/C mice. SE rapidly induced anorexia, and after 12 weeks, SE and PF groups were lighter than control animals (23.9 ± 0.2, 25.5 ± 0.5, 26.8 ± 0.4 g respectively, P < 0.05). White fat (WAT) masses were reduced by both SE and PF. Plasma leptin and insulin were reduced in SE mice; insulin was further reduced by PF. Brown fat UCP1 and 3 mRNA were increased in SE animals relative to PF animals, possibly promoting thermogenesis. WAT mRNA expression of the inflammatory cytokine, TNFα was doubled by SE, while IL-6 was reduced by both PF and SE. Hypothalamic NPY content was increased by SE (89.3 ± 2.8 vs. 75.9 ± 2.4 ng control, P < 0.05), and more by PF (100.7 ± 3.4 ng, P < 0.05 compared to both groups), suggesting disinhibition due to reduced adipose derived leptin. In contrast to equivalent food restriction, cigarette smoke exposure reduced body weight and total hypothalamic NPY, and increased thermogenesis and markers of inflammation. The suppressed hypothalamic NPY and increased UCPs may contribute to the spontaneous hypophagia and extra weight loss in SE animals. These findings contribute to our understanding of weight loss in smoking-related lung disease, suggesting a greater impact than that due to anorexia alone.

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Research paperIncreases in plasma neuropeptide Y concentrations during sympathetic activation in man

Abstract

Lancet

Reg. Peptides

Reg. Peptides

Neuroscience

Neurosci. Lett.

Reg. Peptides

Biochem. Biophys. Res. Commun.

Neurosci. Lett.

Brain Res.

J. Chromatogr.

Physiological responses to maximal exercise in a normal Australian population — comparative values in patients with anatomically defined coronary artery disease

A.N.Z.J. Med.

Research paper
Increases in plasma neuropeptide Y concentrations during sympathetic activation in man