neuropeptide-y and Acute-Disease

While enterocyte secretion is the predominant mechanism considered responsible for secretory diarrhea in response to acute enteric infections, there are several lines of evidence that support alternative mechanisms controlling fluid and electrolyte secretion in diarrhea.. To review enteroendocrine and neuronal mechanisms that participate in the development of acute infectious diarrhea.. Acute infectious diarrheas due to bacterial toxins (e.g., cholera, E. coli heat-stable enterotoxin, C. difficile) and rotavirus are all associated with secretion of transmitters from enteroendocrine cells (e.g., 5-HT) and activation of afferent neurons that stimulate submucosal secretomotor neurons. The latter secrete acetylcholine (which binds to muscarinic receptors on epithelial cells) and VIP. Involvement of nerves was demonstrated by inhibition of bacterial toxin-induced secretion by hexamethonium (nicotinic), tetrodotoxin (Na(+) channel blocker), and lidocaine (visceral/mucosal afferents). Nicotinic receptors are present on secretomotoneurons and these are activated by release of acetylcholine from enteric interneurons or extrinsic efferent fibers. Specific organisms also modify other mechanisms that may contribute to development of acute diarrhea. Thus, mucin secretion, activation of motor mechanisms, increased mucosal permeability and inhibition of bile acid absorption have been reported in specific types of acute infectious diarrhea.. New therapies targeting neural and transmitter mediation including 5-HT, VIP, NPY, as well as toxin receptors and channels activated during acute infectious diarrhea could usher in a novel approach to enhancing glucose-electrolyte solutions used in the treatment of acute diarrhea.

Topics: Acute Disease; Bacterial Toxins; Dysentery; Enteroendocrine Cells; Humans; Neurons, Afferent; Neuropeptide Y; Serotonin; Vasoactive Intestinal Peptide

Low-grade inflammation persists in patients with acute pancreatitis (AP) after hospital discharge, and is linked to metabolic disorders. Neuropeptide Y (NPY) is well recognized as an important mediator of inflammation in these patients but the role of the other two structurally similar peptides, pancreatic polypeptide (PP) and peptide YY (PYY), in inflammation has been sparsely investigated. The aim was to investigate the association between PYY, PP, NPY and circulating levels of innate cytokines in patients after AP.. Fasting blood samples were collected to measure PYY (ng/mL), PP (ng/mL), NPY (pg/mL), interleukin-6 (IL-6) (ng/mL), monocyte chemoattractant protein (MCP) 1 (ng/mL), and tumour necrosis factor (TNF) α (ng/mL). Modified Poisson regression analysis and linear regression analyses were conducted. Age, sex, ethnicity, obesity, diabetes, aetiology, time from 1st attack of AP, recurrence, severity, physical activity, and smoking were adjusted for in several statistical models. P<0.05 was considered statistically significant.. A total of 93 patients were recruited. Peptide YY was significantly associated (p<0.001) with IL-6, MCP-1, and TNFα in the unadjusted and all adjusted models. Pancreatic polypeptide was significantly associated (p<0.001) with IL-6, MCP-1, and TNFα in the unadjusted and at least one adjusted model. Peptide YY and PP together contributed 22.2%, 72.7%, and 34.6% to the variance of IL-6, MCP-1, and TNFα, respectively. Neuropeptide Y was not significantly associated with any of the three cytokines.. Peptide YY and PP are associated with circulating innate pro-inflammatory cytokines in patients after AP and cumulatively contribute to nearly half of the variance of IL-6, MCP-1, and TNFα. Future research is warranted to investigate the signaling pathways that underlie these associations.

Topics: Acute Disease; Adult; Aged; Cytokines; Fasting; Female; Follow-Up Studies; Humans; Immunity, Innate; Male; Middle Aged; Neuropeptide Y; Pancreatic Polypeptide; Pancreatitis; Peptide YY

Few studies have described how neurohormonal activation is influenced by treatment with beta-receptor antagonists in patients with heart failure after acute myocardial infarction. The aims were to describe neurohormonal activity in relation to other variables and to investigate treatment effects of a beta(1) receptor-antagonist compared to a partial beta(1) receptor-agonist.. Double-blind, randomized comparison of metoprolol 50-100 mg b.i.d. (n=74), and xamoterol 100-200 mg b.i.d (n=67). Catecholamines, neuropeptide Y-like immunoreactivity (NPY-LI), renin activity, and N-terminal pro-atrial natriuretic factor (N-ANF) were measured in venous plasma before discharge and after 3 months. Clinical and echocardiographic variables were assessed.. N-ANF showed the closest correlations to clinical and echocardiographic measures of heart failure severity, e.g. NYHA functional class, furosemide dose, exercise tolerance, systolic and diastolic function. Plasma norepinephrine, dopamine and renin activity decreased after 3 months on both treatments, in contrast to a small increase in NPY-LI which was greater (by 3.9 pmol/l, 95% CI 1.2-6.6) in the metoprolol group. N-ANF increased on metoprolol, and decreased on xamoterol (difference: 408 pmol/l, 95% CI 209-607). Increase above median of NPY-LI (>25.2 pmol/l, odds ratio 2.8, P=0.0050) and N-ANF (>1043 pmol/l, odds ratio 2.8, P=0.0055) were related to long term (mean follow-up 6.8 years) cardiovascular mortality.. Decreased neurohormonal activity, reflecting both the sympathetic nervous system and the renin-angiotensin system, was found 3 months after an acute myocardial infarction with heart failure treated with beta-receptor antagonists. The small increase in NPY-LI may suggest increased sympathetic activity or reduced clearance from plasma. The observed changes of N-ANF may be explained by changes in cardiac preload, renal function, and differences in beta-receptor mediated inhibition of atrial release of N-ANF. NPY-LI, and N-ANF at discharge were related to long term cardiovascular mortality.

Topics: Acute Disease; Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Chi-Square Distribution; Dopamine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Echocardiography, Doppler; Epinephrine; Female; Follow-Up Studies; Heart Failure; Humans; Male; Metoprolol; Middle Aged; Myocardial Infarction; Neuropeptide Y; Norepinephrine; Probability; Proportional Hazards Models; Prospective Studies; Survival Rate; Treatment Outcome; Xamoterol

To investigate the effects of intravitreal neuropeptide Y (NPY) treatment following acute retinal ischaemia in an in vivo porcine model. In addition, we evaluated the vasoconstrictive potential of NPY on porcine retinal arteries ex vivo.. Twelve pigs underwent induced retinal ischaemia by elevated intraocular pressure clamping the ocular perfusion pressure at 5 mmHg for 2 hr followed by intravitreal injection of NPY or vehicle. After 4 weeks, retinas were evaluated functionally by standard and global-flash multifocal electroretinogram (mfERG) and histologically by thickness of retinal layers and number of ganglion cells. Additionally, the vasoconstrictive effects of NPY and its involved receptors were tested using wire myographs and NPY receptor antagonists on porcine retinal arteries.. Intravitreal injection of NPY after induced ischaemia caused a significant reduction in the mean induced component (IC) amplitude ratio (treated/normal eye) compared to vehicle-treated eyes. This reduction was accompanied by histological damage, where NPY treatment reduced the mean thickness of inner retinal layers and number of ganglion cells. In retinal arteries, NPY-induced vasoconstriction to a plateau of approximately 65% of potassium-induced constriction. This effect appeared to be mediated via Y1 and Y2, but not Y5.. In seeming contrast to previous in vitro studies, intravitreal NPY treatment caused functional and histological damage compared to vehicle after a retinal ischaemic insult. Furthermore, we showed for the first time that NPY induces Y1- and Y2- but not Y5-mediated vasoconstriction in retinal arteries. This constriction could explain the worsening in vivo effect induced by NPY treatment following an ischaemic insult and suggests that future studies on exploring the neuroprotective effects of NPY might focus on other receptors than Y1 and Y2.

Topics: Acute Disease; Animals; Disease Models, Animal; Electroretinography; Female; Intravitreal Injections; Ischemia; Neuropeptide Y; Retinal Diseases; Retinal Ganglion Cells; Retinal Vessels; Swine; Vasoconstriction

This study tested the hypothesis that neuropeptide Y (NPY) and NPY receptors 1 (Y1) and 2 (Y2) participate in lung allograft rejection. Inflammation in grafts may include interaction between blood leukocytes and graft endothelial cells and marked accumulation of intravascular blood leukocytes. Fewer leukocytes accumulate in lung than in kidney allografts. Lung transplantion was performed in the Dark Agouti to Lewis rat strain combination. Intravascular and intraalveolar leukocytes were isolated from the grafts, and we evaluated the mRNA expression of NPY, Y1, and Y2 by real-time RT-PCR as well as the peptide expression of NPY by radioimmunoassay and immunohistochemistry. NPY and Y1 were expressed by pulmonary intravascular and intraalveolar leukocytes. Y1 was up-regulated by pulmonary intravascular and intraalveolar leukocytes during allograft rejection while Y2 could not be detected. Higher NPY expression levels in intravascular leukocytes were observed in lung compared to kidney allografts, which were investigated previously. Our findings suggest that an increased leukocytic expression of NPY in lung compared to kidney allografts results in a reduced accumulation of leukocytes in allograft vessels.

Topics: Acute Disease; Allografts; Animals; Gene Expression Regulation; Graft Rejection; Leukocytes; Lung; Lung Transplantation; Neuropeptide Y; Rats; Rats, Inbred Lew; Receptors, G-Protein-Coupled; Receptors, Neuropeptide; Receptors, Neuropeptide Y

Peptide YY (PYY) antisecretory effect on intestinal epithelia is well established, whereas less is known about its actions to influence colonic motility in conscious animals. We characterized changes in basal function and stimulated colonic motor function induced by PYY-related peptides in conscious mice. PYY(3-36), PYY, and neuropeptide Y (NPY) (8 nmol/kg) injected intraperitoneally inhibited fecal pellet output (FPO) per hour during novel environment stress by 90%, 63%, and 57%, respectively, whereas the Y(1)-preferring agonists, [Pro(34)]PYY and [Leu(31),Pro(34)]NPY, had no effect. Corticotrophin-releasing factor 2 receptor antagonist did not alter PYY(3-36) inhibitory action. PYY and PYY(3-36) significantly reduced restraint-stimulated defecation, and PYY(3-36) inhibited high-amplitude distal colonic contractions in restrained conscious mice for 1 h, by intraluminal pressure with the use of a microtransducer. PYY suppression of intraperitoneal 5-hydroxytryptophan induced FPO and diarrhea was blocked by the Y(2) antagonist, BIIE0246, injected intraperitoneally and mimicked by PYY(3-36), but not [Leu(31),Pro(34)]NPY. PYY(3-36) also inhibited bethanechol-stimulated FPO and diarrhea. PYY(3-36) inhibited basal FPO during nocturnal feeding period and light phase in fasted/refed mice for 2-3 h, whereas the reduction of food intake lasted for only 1 h. PYY(3-36) delayed gastric emptying after fasting-refeeding by 48% and distal colonic transit time by 104%, whereas [Leu(31),Pro(34)]NPY had no effect. In the proximal and distal colon, higher Y(2) mRNA expression was detected in the mucosa than in muscle layers, and Y(2) immunoreactivity was located in nerve terminals around myenteric neurons. These data established that PYY/PYY(3-36) potently inhibits basal and stress/serotonin/cholinergic-stimulated propulsive colonic motor function in conscious mice, likely via Y(2) receptors.

Topics: 5-Hydroxytryptophan; Acute Disease; Animals; Arginine; Benzazepines; Bethanechol; Colon; Consciousness; Diarrhea; Eating; Efferent Pathways; Gastric Emptying; Gastrointestinal Motility; Male; Mice; Mice, Inbred C57BL; Myenteric Plexus; Neuropeptide Y; Parasympathomimetics; Peptide Fragments; Peptide YY; Receptors, Neuropeptide Y; Restraint, Physical; Stress, Physiological

The objective of the present study was to investigate the effect of acute exposure to electric tail shock stress (ES) and a stress witnessing procedure (SW), as models for physical and psychological stress paradigms, respectively on adherence, phagocytosis and hydrogen peroxide (H(2)O(2)) release from rat peritoneal macrophages. In addition, we studied the in vitro effects of corticosterone (CORT), neuropeptide Y (NPY) and beta-endorphin (BE) on adherence, phagocytosis and H(2)O(2) release from macrophages isolated from control rats and from rats that had been exposed to ES or SW procedures 24 h earlier. ES and SW comparably diminished phagocytosis and H(2)O(2) release, but did not influence macrophage adherence. In vitro treatment with CORT and NPY notably suppressed phagocytosis and potentiated H(2)O(2) release from macrophages. BE suppressed both phagocytosis and H(2)O(2) release from macrophages. Previous exposure to ES and SW altered the responsiveness of the isolated macrophages to their in vitro treatment with mediators of stress, making the cells less sensitive to the influence of CORT and NPY and to a lesser extent to BE. It could be concluded that changes in the local macrophage milieu induced by ES and SW 24 h earlier modify macrophage responses to subsequent in vitro exposure to the stress mimics, CORT, NPY and BE.

Topics: Acute Disease; Animals; beta-Endorphin; Cell Adhesion; Cells, Cultured; Corticosterone; Electroshock; Hydrogen Peroxide; Macrophages, Peritoneal; Male; Neuropeptide Y; Phagocytosis; Rats; Rats, Inbred Strains; Stress, Physiological; Stress, Psychological; Tail

Neuropeptides participate in the pathophysiology of cerebral inflammatory diseases. We analyzed the involvement of neuropeptide Y (NPY) in rat brain infected with Borna Disease Virus (BDV). NPY expressing cerebrocortical neurons were increased during the acute stage of BDV-induced encephalitis. The increase was resistant to immunosuppression by systemic dexamethasone, which greatly reduced inflammatory reactions in the brain. This indicates that the increase of cerebrocortical NPY expression is not causally related to inflammation. As cerebral NPY is known to be increased during experimental seizures and to have anticonvulsive actions, we propose that NPY up-regulated during BDV encephalitis limits seizures known to be associated with Borna Disease.

Topics: Acute Disease; Animals; Borna Disease; Cerebral Cortex; Dexamethasone; Immunosuppressive Agents; Neurons; Neuropeptide Y; Organ Specificity; Rats; Rats, Inbred Lew; Up-Regulation

This study investigated the effects of fetal treatment with dexamethasone on ovine fetal cardiovascular defence responses to acute hypoxaemia, occurring either during or 48 h following the period of glucocorticoid exposure. To address the mechanisms underlying these responses, chemoreflex function and plasma concentrations of catecholamines, neuropeptide Y (NPY) and vasopressin were measured. Under general halothane anaesthesia, 26 Welsh Mountain sheep fetuses were surgically prepared for long-term recording at between 117 and 120 days of gestation (dGA; term is approximately 145 days) with vascular catheters and a Transonic flow probe around a femoral artery. Following at least 5 days of recovery, fetuses were randomly assigned to one of two experimental groups. After 48 h of baseline recording, at 125 +/- 1 dGA, half of the fetuses (n = 13) were continuously infused I.V. with dexamethasone for 48 h at a rate of 2.06 +/- 0.13 microg kg-1 h-1. The remaining 13 fetuses were infused with heparinized saline at the same rate (controls). At 127 +/- 1 dGA, 2 days from the onset of infusions, seven fetuses from each group were subjected to 1 h of acute hypoxaemia. At 129 +/- 1 dGA, 2 days after the end of infusions, six fetuses from each group were subjected to 1 h of acute hypoxaemia. Similar reductions in fetal partial pressure of arterial oxygen occurred in control and dexamethasone-treated fetuses during the acute hypoxaemia protocols. In control fetuses, acute hypoxaemia led to transient bradycardia, femoral vasoconstriction and significant increases in plasma concentrations of catecholamines, vasopressin and NPY. In fetuses subjected to acute hypoxaemia during dexamethasone treatment, the increase in plasma NPY was enhanced, the bradycardic response was prolonged, and the plasma catecholamine and vasopressin responses were diminished. In fetuses subjected to acute hypoxaemia 48 h following dexamethasone treatment, femoral vasoconstriction and plasma catecholamine and vasopressin responses were enhanced, whilst the prolonged bradycardia and augmented plasma NPY responses persisted. These data show that fetal treatment with dexamethasone modifies the pattern and magnitude of fetal cardiovascular responses to acute oxygen deprivation. Modifications to different mechanisms mediating the fetal defence responses to acute hypoxaemia that occur during dexamethasone treatment may reverse, persist or even become enhanced by 48 h following the treatment period.

Topics: Acid-Base Equilibrium; Acute Disease; Animals; Blood Pressure; Carbon Dioxide; Catecholamines; Chemoreceptor Cells; Dexamethasone; Endocrine System; Female; Fetus; Glucocorticoids; Heart Rate, Fetal; Hypoxia; Neuropeptide Y; Oxygen; Pregnancy; Regional Blood Flow; Sheep; Vascular Resistance; Vasopressins

Inflammation induces an up-regulation of neuropeptide tyrosine (NPY) and its receptors in the dorsal horn, suggesting an important role in nociceptive transmission. Our initial studies revealed that NPY dose-dependently increased hotplate response latency, and to a lesser degree, thermal paw withdrawal latency (PWL); these effects occurred at doses that affect neither motor coordination (as assessed by the rotarod test) nor paw skin temperature. We next evaluated the behavioral effects of intrathecal administration of NPY and NPY antagonists with the aim of assessing the contribution of NPY to correlates of persistent nociception associated with the unilateral plantar injection of carrageenan or complete Freund's adjuvant (CFA). NPY robustly and dose-dependently increased PWL on the side ipsilateral to carrageenan injection, with only a small effect on the contralateral side. Similarly, NPY (30 microg) produced a large and long-lasting increase in PWL on the side ipsilateral to CFA injection (140% change), with only a small effect on the contralateral side (25% change). The ipsilateral effect of NPY was completely inhibited with the potent Y1 antagonist, BIBO 3304 (3 microg), but not the Y2 antagonist, BIIE 0246. When administered alone, BIBO 3304 (but not BIIE 0246) slightly decreased thermal PWL on the side ipsilateral (25% change), but not contralateral, to CFA injection; this suggests that inflammation strengthens inhibitory NPY tone. We conclude that spinal Y1 receptors contribute to the inhibitory effects of NPY on thermal hypersensitivity in the awake rat. Further studies are necessary to determine whether enhanced release of NPY and Y1-mediated inhibition of spinal nociceptive transmission ultimately results in a compensatory, adaptive inhibition of thermal hypersensitivity in the setting of inflammation.

Topics: Acute Disease; Animals; Arginine; Body Temperature; Carrageenan; Disease Models, Animal; Freund's Adjuvant; Hot Temperature; Hyperalgesia; Injections, Spinal; Male; Motor Activity; Neurogenic Inflammation; Neuropeptide Y; Rats; Rats, Sprague-Dawley; Receptors, Neuropeptide Y; Spinal Cord

1. The pylorus plays an important role in the regulation of gastric emptying. In addition to the autonomic neuropathy associated with long-standing diabetes, acute hyperglycaemia per se has effects on gastric emptying. In this study, the role of the central nervous system in modulating the effects of hyperglycaemia on gastric distension-induced pyloric relaxation was investigated. 2. Gastric distension-induced pyloric relaxation was significantly reduced by subdiaphragmatic vagotomy, hexamethonium (20 mg kg(-1)) and N (G)-nitro-L-arginine methyl ester (L-NAME; 10 mg kg(-1)), a nitric oxide synthase (NOS) biosynthesis inhibitor, in anaesthetized rats. In contrast, neither splanchnectomy nor guanethidine (5 mg kg(-1)) had an effect. 3. An intravenous (I.V.) infusion of D-glucose (20 %) for 30 min, which increased blood glucose concentrations from 5.4 to 12.8 mM, significantly inhibited gastric distension-induced pyloric relaxation. 4. An intracerebroventricular (I.C.V.) injection of D-glucose (3 micromol) also significantly inhibited gastric distension-induced pyloric relaxation without affecting peripheral blood glucose concentrations. 5. I.V. infusion of D-glucose significantly elevated hypothalamic neuropeptide Y (NPY) concentrations. 6. Intracerebroventricular (I.C.V.) administration of NPY (0.03--3 nmol) and a Y1 receptor agonist, [leu(31), pro(34)] NPY (0.03--3 nmol), significantly inhibited gastric distension-induced pyloric relaxation in a dose-dependent manner. 7. I.C.V. administration of a Y1 receptor antagonist, BIBP 3226 (30 nmol), and of a NPY antibody (titre 1:24 000, 3 microl) abolished the inhibitory effects of hyperglycaemia on gastric distension-induced pyloric relaxation. 8. Taken together, these findings suggest that gastric distension-induced pyloric relaxation is mediated via a vago-vagal reflex and NO release. Acute hyperglycaemia stimulates hypothalamic NPY release, which, acting through the Y1 receptor, inhibits gastric distension-induced pyloric relaxation in rats exposed to acute elevations in blood glucose concentrations.

Topics: Acute Disease; Animals; Arginine; Catheterization; Central Nervous System; Electrophysiology; Hyperglycemia; Hypothalamus; Injections, Intraventricular; Male; Muscle Relaxation; Muscle, Smooth; Neuropeptide Y; Pylorus; Rats; Rats, Sprague-Dawley; Receptors, Neuropeptide Y; Reference Values; Stomach

Inflammatory processes may play a critical role in the degeneration of basal forebrain cholinergic cells that underlies some of the cognitive impairments associated with Alzheimer's disease. In the present study, the proinflammagen lipopolysaccharide, from the cell wall of Gram-negative bacteria, was used to produce inflammation within the basal forebrain of rats. The effects of acute, high-dose injections of lipopolysaccharide (2, 20 or 40 microg) upon basal forebrain chemistry and neuronal integrity were compared with the effects of chronic, low-dose lipopolysaccharide infusions (0.18, 0.25, 1.8 or 5.0 microg/h) for either 14, 37, 74 or 112 days. Acute exposure to lipopolysaccharide decreased cortical choline acetyltransferase activity and the number of immunoreactive choline acetyltransferase-positive cells within a small region of the basal forebrain. Regional levels of five different neuropeptides were unchanged by acute, high-dose lipopolysaccharide injections. Chronic lipopolysaccharide infusions produced (i) a time-dependent, but not dose-dependent, decrease in cortical choline acetyltransferase activity that paralleled a decline in the number of choline acetyltransferase- and p75-immunoreactive cells within the basal forebrain, and (ii) a dense distribution of reactive astrocytes and microglia within the basal forebrain. Chronic neuroinflammation might underlie the genesis of some neuropathological changes associated with normal ageing or Alzheimer's disease.

Topics: Acute Disease; Animals; Cerebral Cortex; Choline O-Acetyltransferase; Chronic Disease; Escherichia coli; Galanin; Inflammation; Lipopolysaccharides; Male; Neurokinin B; Neuropeptide Y; Neuropeptides; Neurotensin; Prosencephalon; Rats; Rats, Inbred F344; Somatostatin; Time Factors

Seizures increase the synthesis of brain-derived neurotrophic factor in forebrain areas, suggesting this neurotrophin has biological actions in epileptic tissue. The understanding of these actions requires information on the sites and extent of brain-derived neurotrophic factor production in areas involved in seizures onset and their spread. In this study, we investigated by immunocytochemistry the changes in brain-derived neurotrophic factor in the hippocampus, entorhinal and perirhinal cortices of rats at increasing times after acute seizures eventually leading to spontaneous convulsions. We also tested the hypothesis that seizure-induced changes in brain-derived neurotrophic factor induce later modifications in neuropeptide Y expression by comparing, in each instance, their immunoreactive patterns. As early as 100 min after seizure induction, brain-derived neurotrophic factor immunoreactivity increased in CA1 pyramidal and granule neurons and in cells of layers II-III of the entorhinal cortex. At later times, immunoreactivity progressively decreased in somata while increasing in fibres in the hippocampus, the subicular complex and in specific layers of the entorhinal and perirhinal cortices. Changes in neuropeptide Y immunoreactivity were superimposed upon and closely followed those of brain-derived neurotrophic factor. One week after seizure induction, brain-derived neurotrophic factor and neuropeptide Y immunoreactivities were similar to controls in 50% of rats. In rats experiencing spontaneous convulsions, brain-derived neurotrophic factor and neuropeptide Y immunoreactivity was strongly enhanced in fibres in the hippocampus/parahippocampal gyrus and in the temporal cortex. In the dentate gyrus, changes in immunoreactivity depended on sprouting of mossy fibres as assessed by growth-associated protein-43-immunoreactivity. These modifications were inhibited by repeated anticonvulsant treatment with phenobarbital. The dynamic and temporally-linked alterations in brain-derived neurotrophic factor and neuropeptide Y in brain regions critically involved in epileptogenesis suggest a functional link between these two substances in the regulation of network excitability.

Topics: Acute Disease; Animals; Anticonvulsants; Brain; Brain-Derived Neurotrophic Factor; Colchicine; Electroencephalography; Epilepsy; Immunohistochemistry; Limbic System; Male; Neuropeptide Y; Phenobarbital; Rats; Rats, Sprague-Dawley; Status Epilepticus; Time Factors

1. Hormones involved in cardiovascular regulation are influenced by drug treatment. It is therefore difficult to study endocrine mechanisms in heart failure as most patients are already on treatment by the time they reach hospital. 2. We studied nine hospital in-patients before and after treatment of acute New York Heart Association class IV heart failure. 3. Before treatment, plasma brain and atrial natriuretic peptides were markedly elevated (BNP 121 +/- 26 pg/ml, ANP 163 +/- 33 pg/ml; normal range: BNP 3.9 +/- 0.3 pg/ml, ANP 8.6 +/- 0.8 pg/ml) and correlated positively with serum creatinine and left ventricular end-diastolic diameter and negatively with ejection fraction. Eight patients improved and one died. 4. With improvement plasma ANP and BNP fell. Initial renin activity was within the normal range but increased on treatment. Plasma neuropeptide Y and adrenaline remained normal before and after treatment in the eight patients who improved. Initial plasma noradrenaline was in the normal range in four of these patients and just above normal in a further four. In the patient who died, initial plasma neuropeptide Y and catecholamines were very high. 5. Plasma BNP emerged as complementary to ANP as a dynamic index in severe heart failure; however, renal function is also an important determinant of plasma BNP and ANP. There is little evidence for activation of the circulating renin-angiotensin-aldosterone system or neuropeptide Y before treatment of acute heart failure.

Topics: Acute Disease; Aged; Aged, 80 and over; Aldosterone; Atrial Natriuretic Factor; Biomarkers; Diuretics; Epinephrine; Female; Furosemide; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Neuropeptide Y; Norepinephrine; Renin; Severity of Illness Index

Hypoglycemia causes hyperphagia and weight gain, through unknown peripheral and central signals. We investigated the effect of hypoglycemia on NPY and leptin expression and the ability of leptin to inhibit hypoglycemia-induced hyperphagia. Acute hypoglycemia (60 U/kg SC insulin; n = 8) increased food intake (p < 0.01) compared with controls (n = 8). Insulin- and leptin-treated rats (300 microg/kg IP leptin; n = 8) had reduced hyperphagia (p < 0.05 vs. controls; p < 0.05 vs. insulin alone) and a 15% fall in NPY mRNA levels compared with controls (p < 0.01). Chronic hypoglycemia, (20-60 U/kg/day insulin; n = 8) increased food intake compared with vehicle-treated controls (p < 0.01). Leptin and insulin administration (300 microg/kg/day IP leptin; n = 8) reduced hyperphagia (p < 0.01 vs. controls, p < 0.05 vs. insulin alone), and NPY mRNA fell by 18% vs. controls (p < 0.01). We conclude that hypoglycemia-induced hyperphagia is not mediated by either a fall in leptin or an increase in hypothalamic NPY mRNA. Leptin can inhibit feeding in hyperphagic hypoglycemic rats, and this may partly be attributable to its inhibition of the NPY neurons.

Topics: Acute Disease; Analysis of Variance; Animals; Arcuate Nucleus of Hypothalamus; Blood Glucose; Body Weight; Chronic Disease; Eating; Hyperphagia; Hypoglycemia; Insulin; Leptin; Male; Models, Biological; Neuropeptide Y; Protein Biosynthesis; Proteins; Rats; Rats, Wistar; RNA, Messenger

We examined the effect of streptozotocin-induced maternal diabetes of 6-day duration and 4- to 24-h intracerebroventricular and systemic hyperinsulinism on fetal brain neuropeptide Y (NPY) synthesis and concentrations. Maternal diabetes (n = 6) leading to fetal hyperglycemia (5-fold increase; P < 0.05) and normoinsulinemia caused a 40% decline (P < 0.05) in fetal brain NPY messenger RNA (mRNA) and a 50% decline (P < 0.05) in NPY radioimmunoassayable levels compared to levels in streptozotocin-treated nondiabetic (n = 7) and vehicle-treated control (n = 8) animals. In contrast, systemic hyperinsulinemia (n = 7) of 5- to 100-fold increase (P < 0.05) over the respective control (n = 7) with normoglycemia caused an insignificant (20-30%) decrease in fetal brain NPY mRNA and protein concentrations. However, fetal intracerebroventricular hyperinsulinism (n = 7) with no change in fetal glucose concentrations caused a 50-60% decline (P < 0.05) in only the NPY peptide levels, with no change in the corresponding mRNA amounts. We conclude that fetal hyperglycemia of 6-day duration and intracerebroventricular hyperinsulinism of 4-24 h suppress fetal brain NPY concentrations, the former by a pretranslational and the latter by either a translational/posttranslational mechanism or depletion of intracellular secretory stores. We speculate that fetal hyperglycemia and intracerebroventricular hyperinsulinism additively can inhibit various intrauterine and immediate postnatal NPY-mediated biological functions.

Topics: Acute Disease; Animals; Brain; Brain Diseases; Female; Fetal Diseases; Fetus; Hyperglycemia; Hyperinsulinism; Neuropeptide Y; Osmolar Concentration; Pregnancy; Pregnancy in Diabetics; Rats; Rats, Sprague-Dawley

In a recent study we have shown a bilateral release of substance P (SP)-, neurokinin A (NKA)-, calcitonin gene-related peptide (CGRP)- and neuropeptide Y (NPY)-like immunoreactivity (-LI) in rat synovial fluid during acute monoarthritis. In order to elucidate the mechanisms underlying these phenomena, we examined the correlation between neuropeptide-LI in rat cerebrospinal fluid (CSF) and synovial fluid and between plasma and synovial fluid following the intra-articular injection of equal volumes (0.05 ml) of either Freund's adjuvans, carrageenan 2%, substance P 10(-5) M or human recombinant interleukin-1 alpha. Control rats were given saline intra-articularly. CSF, plasma and synovial fluid from the knee joints were obtained at 2, 6 and 24 h after injection and were analysed by specific radioimmunoassays. The intra-articular injection of pro-inflammatory substances induced changes in neuropeptide-LI in synovial fluid, CSF and plasma. However, there was no correlation between neuropeptide-LI in synovial fluid and plasma or between synovial fluid and CSF. The results of the present study does not support the hypothesis that the bilateral changes in neuropeptide-LI in synovial fluid were due to a release of neuropeptides from the inflamed joint into the systemic circulation. However, in carrageenan induced inflammation there was a tendency towards a correlation in SP-LI between CSF and synovial fluid suggesting that central neurogenic mechanisms should be studied in order to explain the bilateral changes seen.

Topics: Acute Disease; Animals; Arthritis; Calcitonin Gene-Related Peptide; Knee Joint; Male; Neurokinin A; Neuropeptide Y; Neuropeptides; Osmolar Concentration; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Substance P; Synovial Fluid

Neuropeptide Y is a co-transmitter with noradrenaline in sympathetic neurons supplying arteries and veins with potent contractile effects. To investigate the role of neuropeptide Y in hypertension, we measured the circulating levels of neuropeptide Y and noradrenaline in patients with severe hypertension.. Samples were collected from patients with untreated, severe hypertension (diastolic blood pressure > 120 mmHg) and in age- and sex-matched controls. After treatment with beta-adrenoceptor blockers, diuretics, angiotensin converting enzyme inhibitors of calcium antagonists, samples were taken from the patients during 12 months.. The circulating levels of neuropeptide Y-like immunoreactivity (NPY-LI) were measured with a radioimmunoassay using a rabbit antiserum. Catecholamines were measured using high-performance liquid chromatography and electrochemical detection.. There was a significantly higher level of NPY-LI in the patients when they were compared with the controls. However, there was no correlation either in the controls or in the hypertensives between systolic blood pressure, diastolic blood pressure and NPY-LI or noradrenaline. The increased level of NPY-LI in plasma remained elevated for up to 12 months despite reduction in blood pressure to acceptable levels. The noradrenaline level was not increased before treatment, after 2-4 weeks or after 2-12 months treatment.. The high level of NPY-LI may represent a marker for higher activity of the sympathetic nervous system which is not controlled by the treatment of blood pressure to normotension.

Topics: Acute Disease; Adult; Age Factors; Antihypertensive Agents; Blood Pressure; Case-Control Studies; Epinephrine; Female; Follow-Up Studies; Humans; Hypertension; Male; Middle Aged; Neuropeptide Y; Norepinephrine

A possible role of platelet-derived 5-HT was examined concerning the pathogenesis of cerebral vasospasm. Intracisternal injection of 5 ml of platelet-rich plasma (PRP; approximately 7.5 x 10(8) platelets) induced not only acute (1 h) but also chronic (7 days) angiographically evident cerebral vasospasm in dogs. Sympathetic perivascular nerves on cerebral arteries showed no remarkable change following repeated injections of PRP, as the dense distribution of catecholamine-fluorescence and neuropeptide Y-like immunoreactive nerve fibers on Day 7 was comparable to findings in the preinjection controls. While there were no 5-HT-immunoreactive fibers in the cerebral arteries of control animals, numerous 5-HT-immunoreactive fibers were present in the PRP-injected animals. These results suggest that 5-HT, presumably released from extravasated platelets, may be taken up by nerve endings and act as a vasoconstrictor transmitter in the pathogenesis of chronic vasospasm.

Topics: Acute Disease; Animals; Basilar Artery; Blood Platelets; Catecholamines; Chronic Disease; Dogs; Female; Immunohistochemistry; Ischemic Attack, Transient; Male; Muscle, Smooth, Vascular; Neurons; Neuropeptide Y; Serotonin; Subarachnoid Hemorrhage

Bronchoconstriction has been found to cause little sympathoadrenal activation in asthmatic patients. It has been questioned whether this is due to blunted sympatho-adrenal reactivity in asthmatics or if bronchoconstriction is a stimulus for sympatho-adrenal activation at all. We therefore compared sympatho-adrenal responses in eight asthmatic patients and 12 healthy subjects by measurements of plasma adrenaline and noradrenaline concentrations before, during and after methacholine-induced bronchoconstriction. Significant bronchoconstriction was obtained in eight of the healthy subjects and in all of the asthmatics. Considerably higher concentrations of methacholine were required to evoke bronchoconstriction in the healthy subjects but the relative magnitudes of bronchoconstriction were similar in the two groups: peak expiratory flow (PEF) decreased by approximately 24 and approximately 28% and specific airway conductance (sGaw) decreased by approximately 68 and approximately 70% in asthmatics and controls, respectively). Methacholine-induced bronchoconstriction did not alter plasma catecholamine levels significantly in either group. In addition, plasma concentrations of catecholamines and neuropeptide Y-like immunoreactivity (NPY-LI) were measured before and during bronchoconstriction induced by histamine or allergen in 8 and 5 asthmatic subjects, respectively. Plasma noradrenaline, adrenaline and NPY-LI remained unchanged up to 30 min after bronchoconstriction induced by histamine or allergen. We, therefore, conclude that bronchoconstriction is not a stimulus for sympatho-adrenal activation and that the lack of an adrenaline response to bronchoconstriction is not likely to be related to NPY release.

Topics: Acute Disease; Adolescent; Adult; Asthma; Bronchi; Bronchial Provocation Tests; Bronchial Spasm; Epinephrine; Female; Humans; Male; Methacholine Chloride; Methacholine Compounds; Middle Aged; Neuropeptide Y; Norepinephrine; Reference Values; Respiratory Function Tests

Twenty-five elderly asthmatic patients attending the internal medicine emergency ward because of an acute exacerbation of asthma were sampled, prior to acute treatment, for determination of systemic venous plasma levels of noradrenaline (NA), adrenaline (A) and neuropeptide Y-like immunoreactivity (NPY-LI). Whereas NA and NPY-LI were about two-fold higher than control values, plasma A levels were not significantly increased. Twelve of the asthmatic patients were also tested at resting stable conditions and were essentially asymptomatic. All values were then similar to those of control subjects (n = 28) except for a significantly higher NPY-LI plasma level in asthmatics. In seven of these patients a near maximal physical exercise test caused significantly increased NA, A and NPY-LI plasma levels. It is concluded that the acute asthma attack is associated with elevated NA and NPY-LI plasma levels, but an impaired A response. Furthermore, that circulating NPY under these conditions has a nervous rather than adrenal origin.

Topics: Acute Disease; Aged; Aged, 80 and over; Asthma; Epinephrine; Female; Humans; Male; Middle Aged; Neuropeptide Y; Rest