Plasma Neuropeptide Y-like Immunoreactivity Research Articles

Neuropeptide Y in Euthymic Lithium-Treated Women with Bipolar Disorder

Plasma neuropeptide Y-like immunoreactivity (NPY-LI) and platelet cyclic AMP (cAMP) activity were determined in 13 women with bipolar disorder stabilized on lithium (Li) and 12 matched healthy controls. No differences in plasma NPY-LI were found between the two groups. In euthymic Li-treated bipolar patients, there was an inverse correlation between plasma NPY-LI levels and intracellular cAMP in prostaglandin E₁-stimulated platelets. A positive correlation was found between plasma NPY-LI levels and age in both the patient and the control group. Our findings support earlier findings that NPY is capable of inhibiting adenylyl cyclase and that aging is a physiological factor in regulating NPY-LI levels.

Effect of neuropeptide Y on hemodynamics of the rabbit lung.

We evaluated the effect of neuropeptide Y (NPY) on the hemodynamics of the isolated rabbit lung perfused at constant flow and outflow pressure. Doses of 10(-8) and 10(-7) M NPY increased pulmonary arterial pressure (Ppa) from 11.5 +/- 1.0 (SE) mmHg to, respectively, 16.4 +/- 1.5 and 26.0 +/- 3.8 mmHg (P < 0.05, n = 5 mmHg lungs), with 78 +/- 4% of the increase at 10(-7) M resulting from an increased arterial resistance. At the latter dose, pulmonary capillary pressure increased from 5.8 +/- 0.9 to 9.4 +/- 1.0 mmHg (P < 0.05). When administered in the presence of norepinephrine, 10(-8) and 10(-7) M NPY (n = 6) produced extreme increases in Ppa to 66.1 +/- 20.5 and 114.7 +/- 25.5 mmHg, respectively, that were due primarily to an increased arterial resistance. To determine the significance of circulating NPY as a pulmonary vasoactive agent, we measured plasma NPY-like immunoreactivity in anesthetized rabbits after massively activating the sympathetic nervous system with veratrine. NPY-like immunoreactivity increased from 74 +/- 10 to 111 +/- 10 (SE) pM (P < 0.05). Thus, although NPY is a potent vasoconstrictor in the rabbit lung, it is not likely that plasma NPY concentrations rise sufficiently, even after massive sympathetic nervous system activation, to produce pulmonary vasoconstriction in the intact rabbit.

14-154 - Human plasma NPY-like immunoreactivity in patients with depressive and panic disorder

14-154 - Human plasma NPY-like immunoreactivity in patients with depressive and panic disorder

Increased neuropeptide Y-like immunoreactivity in cerebrospinal fluid and plasma of human immunodeficiency virus-infected patients: relationship to HIV encephalopathy

Neuropeptide Y (NPY) is one of the most abundant and phylogenetically best conserved peptides in the mammalian central and peripheral nervous system where it plays an important role in the regulation of cardiovascular, metabolic, endocrine, immunological and cognitive functions. In a prospective study we determined neuropeptide Y-like immunoreactivity (NPY-LI) in cerebrospinal fluid (CSF) and plasma of 95 HIV-seropositive ( n = 49) or seronegative ( n = 46) patients who underwent diagnostic CSF examination. CSF and plasma NPY-LI but not noradrenaline concentrations were higher in seropositive than in seronegative patients indicating that raised levels of NPY-LI did not result from a non-specific activation of the sympathetic nervous system. Increased CSF NPY-LI was positively correlated with the degree of HIV encephalopathy ( P < 0.01, Kruskal-Wallis test). Inflammatory disorders of the central nervous system and dementia due to other causes in HIV-seronegative patients were not associated with increased CSF NPY-LI. Our data suggest that increased CSF NPY-LI is a relatively specific phenomenon of HIV encephalopathy and may be involved in the pathogenesis of HIV-related neurological dysfunction. The links between retroviral infection and increased expression of neuropeptide Y and their pathophysiological implications remain to be determined.

Inhibitory effect of propofol on sympathetic neurotransmission results in changes of plasma neuropeptide Y in rats.

1. The effects of propofol on sympathetic neurotransmission and changes of plasma level of neuropeptide Y-like immunoreactivity (NPY-ir) were investigated in rats. 2. Intraperitoneal injection of propofol into rats lowered the systemic blood pressure and plasma NPY-ir in a dose-dependent manner. 3. Decrease of plasma NPY-ir induced by propofol was not modified in adrenalectomized rats. In the activation of adrenergic neurotransmission by a ganglionic nicotinic agonist, elevation of plasma NPY-ir was also reduced by propofol indicating the direct effect on peripheral adrenergic nerve terminals. 4. Plasma level of NPY-ir reversed in parallel with the recovery of anaesthesia induced by propofol. After an intracerebroventricular injection of propofol into the rats, both the lowering of plasma NPY-ir and the induction of anaesthesia were observed. Thus, a central nervous system effect of propofol can also be considered in its effect on plasma NPY-ir. 5. The data suggest that propofol has the ability to lower plasma NPY-ir in rats through an inhibition of adrenergic neurotransmission via central nervous pathway and/or peripheral nerve terminal blockade.

Elevated plasma levels of neuropeptide Y in patients with panic disorder.

Neuropeptide Y is a pancreatic polypeptide closely associated with noradrenergic activity both in the central and peripheral nervous systems. The objective of this study was to assess plasma neuropeptide Y-like immunoreactivity in panic disorder. Radioimmunoassays were performed in 12 patients with DSM-III-R panic disorder and two groups of normal comparison subjects (N = 22 and N = 16). Markedly higher plasma neuropeptide Y-like immunoreactivity was found in patients with panic disorder. Higher plasma neuropeptide Y-like immunoreactivity suggests that this peptide may be implicated in the etiology or expression of symptoms of panic disorder.

Differences in the neuropeptide Y-like immunoreactivity of the plasma and platelets of human volunteers and depressed patients.

In this study, patients with recurrent major depression were found to have significantly lower neuropeptide Y-like immunoreactivity (NPY-LI) in platelet-poor plasma (p < 0.01) and significantly higher NPY-LI in platelets (p < 0.001) compared to controls. Also, qualitative differences in the NPY-LI in platelet-poor plasma (PPP) and platelets were detected when the samples were analyzed by HPLC followed by RIA of the collected fractions.

Changes in plasma concentrations of vasoactive neuropeptides in patients with sepsis and septic shock

The aim of this work was to study the hypothesis that the release of vasoactive neuropeptides may be related to the hemodynamic changes and severity of disease in human sepsis and septic shock. Twenty-two patients diagnosed with sepsis and treated in medical wards with standard supportive therapy and twenty patients admitted to a medical intensive care unit because of septic shock were studied Twenty healthy volunteers in a similar age range were enrolled as control group. Blood samples were taken at onset and every 12 hours on the following day after hospital admission to measure plasma concentrations of calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY) and substance P (SP). Clinical and biochemical variables were measured simultaneously. The Acute Physiology and Chronic Health Evaluation (APACHE) II score was calculated on admission. From the day of admission, septic shock patients had significantly higher plasma CGRP-like immunoreactivity levels than patients with sepsis, as well as both groups of patients compared to control subjects. Plasma NPY-like immunoreactivity levels in patients with either sepsis or septic shock was significantly increased, and plasma SP-like immunoreactivity levels significantly reduced compared to those in controls. Plasma CGRP levels at study entry correlated with the APACHE II score ( r=0.71, p<0.01) , as well as with the cardiac index ( r=0.61, p<0.05) and systemic vascular resistance index ( r=−0.62, p<0.05) . Our data suggest that both CGRP and NPY, but not SP, are increasedly released into the circulation during the development of human sepsis and septic shock. In patients with sepsis the vasoconstriction mediated by the release of NPY appears to counterbalance the vasodilatory effect of CGRP. In septic shock patients, however, the release of NPY might be inadequately low to overcome the widespread CGRP-induced vasodilation.

NEUROPEPTIDE Y IN CORTISOL‐INDUCED HYPERTENSION IN MALE VOLUNTEERS

1. Cortisol-induced blood pressure rises in men are not accompanied by increases in plasma catecholamines. The present study examines the effects of cortisol on the sympathetic co-transmitter, neuropeptide Y (NPY). 2. Eight normal men were given cortisol 200 mg/day over 5 days and haemodynamic, metabolic and hormonal measures were taken. Plasma NPY-like immunoreactivity (NPY-LI) concentrations were measured by direct radio-immunoassay. 3. Cortisol significantly increased systolic, diastolic and mean arterial pressure, bodyweight, plasma glucose and total white cell concentration and decreased plasma potassium and total eosinophil count, as in previous studies. Plasma NPY concentrations were not altered significantly during cortisol treatment, but increased following cessation of cortisol treatment (P = 0.006). 4. The essentially unchanged pattern for NPY concentration with cortisol treatment resembles that previously reported for adrenaline and noradrenaline, but the increase in NPY on cortisol withdrawal was not seen for adrenaline or noradrenaline. These data do not support a role for sympathetic activation in the genesis of cortisol-induced hypertension.

Prognostic value of plasma neuropeptide-Y in coronary care unit patients with and without acute myocardial infarction.

Plasma neuropeptide Y-like immunoreactivity (NPY-LI) is elevated in patients with acute myocardial ischaemia and congestive heart failure (CHF) owing to increased activity of the sympathetic nervous system. The prognostic value of plasma NPY-LI with regard to mortality was studied in 324 random patients admitted to a coronary care unit. The one-year mortality was 37% in 113 patients with acute myocardial infarction (AMI) and 18% in those without AMI. Several factors were tested by multiple logistical regression analysis to predict the one-year mortality. Plasma NPY-LI > 60 pmol.l-1, advanced age and previous CHF were independent prognostic factors for an increased risk of mortality in patients without AMI. The mortality rate after one year in non-AMI patients with plasma NPY-LI < or = 60 pmol.l-1 was 14% compared to 69% in those with plasma NPY-LI > 60 pmol.l-1. Increased heart rate was the only independent prognostic factor for increased mortality in AMI patients. Plasma NPY-LI on admission was an independent predictor of mortality in CCU patients without AMI and thus resembles plasma noradrenaline.

Augmented Resting Sympathetic Activity in Awake Patients With Obstructive Sleep Apnea

Muscle nerve sympathetic activity (MSA) was recorded during wakefulness in 11 patients with obstructive sleep apnea (OSA) and in 9 sex- and age-matched healthy control subjects. Plasma levels of norepinephrine (NE) and neuropeptide Y were analyzed. Five patients had established hypertension (resting supine systolic BP/diastolic BP > or = 160/95 mm Hg). The investigation was performed after a minimum of 3 weeks' washout period of antihypertensive medication. Muscle sympathetic activity during supine rest was higher in patients compared with controls (p < 0.01) with no difference between normotensive and hypertensive patients. However, systolic, but not diastolic, BP was positively related to resting MSA (n = 20, p < 0.01). There was no significant correlation between body mass index and MSA. Resting MSA was unrelated to disease severity expressed as apnea frequency or minimum SaO2 during the overnight recording. Both the arterial and venous plasma norepinephrine was higher in patients compared with controls (p < 0.05). Plasma levels of NE correlated to resting MSA (p < 0.01) in the whole study group (patients and controls) but not within the respective subgroups. No significant correlation, however, was found between plasma NE (arterial and venous) and BP. Plasma neuropeptide Y-like immunoreactivity was similar in patients and controls. However, one patient with hypertension had approximately twice this level in repeated samples. It is concluded that neurogenic sympathetic activity as well as circulating plasma NE is increased in patients with OSA. This increased sympathetic activity during awake supine rest may reflect a pathophysiologic adaptation to hypoxia and hemodynamic changes occurring at repetitive apneas during sleep. The correlation between MSA and systolic BP implies that this mechanism may be directly or indirectly involved in the development of cardiovascular complications in OSA.

Paradoxical decrease in circulating neuropeptide Y-like immunoreactivity during mild orthostatic stress in subjects with and without congestive heart failure.

Neuropeptide Y (NPY) is thought to be co-released with catecholamines in response to major cardiovascular stresses, but its relation to the release of catecholamines in response to minor stresses has been less well described. We therefore studied the response of plasma NPY-like immunoreactivity (NPY-Li) levels to standing (10 min) in eight normal subjects and 11 patients with congestive heart failure, and to short-term (6h) vasodilator therapy in 13 patients with congestive heart failure. In both normal and heart failure patients, NPY-Li-decreased (296 +/- 73 to 233 +/- 63 pg.ml-1 and 652 +/- 36 to 516 +/- 25 pg.ml-1 (P < 0.01) respectively) in response to standing, whereas catecholamines increased in both groups (norepinephrine 203 +/- 73 to 507 +/- 165 pg.ml-1 and 493 +/- 197 to 813 +/- 336 pg.ml-1 (P < 0.001) respectively and epinephrine 23 +/- 12 to 38 +/- 12 pg.ml-1 and 46 +/- 19 to 62 +/- 28 pg.ml-1 (P < 0.001) respectively). Both basal circulating NPY-Li and catecholamine levels were markedly increased in congestive heart failure patients, but catecholamines and NPY-Li did not correlate with each other. After 6 h of nitroglycerin infusion, mean arterial pressure was decreased, but circulating neurohumoral levels remained unchanged and NPY-Li levels decreased (653 +/- 37 to 517 +/- 26 pg.ml-1, P < 0.01). It is concluded that basal circulating NPY-Li and catecholamine levels are increased in congestive heart failure and that this neurohormone could play a concomitant role in the increase in peripheral resistance in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Circulating neuropeptide Y in dog plasma consists of multiple peptide fragments

Neuropeptide Y-like immunoreactivity (NPY-LI) in dog plasma was characterized and quantified using three extraction methods (Sep-Pak:acetonitrile, HCl:ethanol, and ethanol). Sep-Pak extraction yields the best recovery and preserves the integrity of the peptide. Oxidized NPY is not generated during blood collection. Using two antisera of different specificities, at least three peptide forms in normal dog arterial and venous plasma were detected. A peptide with retention times similar to oxidized NPY or peptide YY is the major component of plasma NPY-LI under basal conditions, but NPY(1–36) predominates during sympathetic stimulation. The mature peptide in dog plasma is similar to human NPY. The antiserum ABII provides a more accurate measure of circulating NPY(1–36) and its oxidized form. The antiserum ABI is useful for detecting NPY-like fragments.

Neuropeptide Y-like immunoreactivity and hypertension.

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.

Alterations in circulating levels and cardiovascular tissue content of neuropeptide Y-like immunoreactivity during the development of deoxycorticosterone acetate-salt hypertension in the rat

Objective To investigate the modification of plasma and tissue neuropeptide Y-like immunoreactivity (NPY-li) concentrations, in relation to blood pressure and plasma catecholamine levels, during the development of deoxycorticosterone acetate (DOCA)-salt hypertension. Methods Mean arterial pressure (MAP), heart rate, tissue and plasma NPY-li levels, and aortic norepinephrine and epinephrine plasma levels were measured in conscious DOCA-salt hypertensive rats treated for 1, 2 and 3 weeks, and in their respective normotensive controls. Results Both norepinephrine and NPY-li plasma levels increased significantly in parallel with blood pressure during DOCA-salt treatment, so that MAP was significantly correlated with plasma norepinephrine and NPY-li levels in hypertensive rats. Plasma NPY-li levels were also correlated with norepinephrine levels only in hypertensive rats, but were correlated with epinephrine levels only in normotensive animals. Tissue NPY-li content was lower in the mesenteric artery and heart ventricles after 1–3 weeks of DOCA-salt treatment, but the content in the adrenal gland was not significantly different from that in normotensive rats. Conclusions In DOCA-salt hypertensive rats, increased plasma NPY-li levels originate primarily from the sympathetic nerves, since those levels were correlated exclusively with circulating norepinephrine levels and they were associated with a reduction in NPY-li content of the heart and mesenteric artery. It is thus possible that the enhanced release of NPY-li from sympathetic nerves could contribute to the rise in blood pressure and to the maintenance of hypertension in this experimental model.

Circulating neuropeptide Y does not produce pulmonary hypertension during massive sympathetic activation

We tested the possibility that neuropeptide Y (NPY) may contribute to the pulmonary hypertension that occurs after massive sympathetic activation produced by intracisternal veratrine administration in the chloralose-anesthetized dog. In six dogs, veratrine caused arterial NPY-like immunoreactivity (NPY-LI) to rise from 873 +/- 150 (SE) pg/ml to peak values of 3,780 +/- 666 pg/ml by 60-120 min. (In 3 animals, adrenalectomy significantly reduced the increases in NPY-LI.) In five additional dogs, we infused porcine NPY for 30 min in doses that increased arterial NPY-LI to 8,354 +/- 1,514 pg/ml and observed only minor changes in pulmonary hemodynamics. In three isolated perfused canine left lower lung lobe (LLL) preparations, increasing doses of NPY were administered, producing levels of plasma NPY-LI, at the highest dose, that exceeded those observed after veratrine administration by three orders of magnitude. No changes in LLL arterial or double-occlusion capillary pressures were observed at any dose. Similarly, no changes in LLL hemodynamics were observed in three additional lobes when NPY was administered while norepinephrine was being infused. We conclude that it is unlikely that NPY plays a role as a circulating vasoactive agent in producing the pulmonary hypertension and edema that occur in this model.

Increase of plasma neuropeptide Y-like immunoreactivity following chronic hypoxia in the rat.

In an attempt to understand the changes of circulating neuropeptide Y (NPY) during hypoxia, the plasma level of NPY was investigated by radioimmunoassay. Exposure of rats to hypobaric hypoxia at an altitude of 18,000 ft for 4 weeks causes an increase of pulmonary pressure and an elevation of plasma NPY-like immunoreactivity (NPY-LI). However, the systemic blood pressure was not elevated by this chronic hypoxia. Also, plasma noradrenaline (NA) estimated by chromatographic analysis (HPLC-ECD) was not markedly raised. Failure of bretylium and guanethidine, sympathetic neuron blockers, in reducing the plasma NPY-LI level of these rats ruled out the participation of adrenergic nervous terminals. Adrenal medulla seems responsible for this elevation of plasma NPY-LI because this magnitude disappeared in adrenalectomized rats. These data suggest that chronic hypoxia induced an elevation of circulating NPY from the adrenal gland of rats.

Splanchnic and renal vasoconstrictor and metabolic responses to neuropeptide Y in resting and exercising man.

The local clearance of neuropeptide Y (NPY) and whether NPY influences splanchnic and renal metabolism in man have not been investigated previously. The influence of NPY on splanchnic and renal blood flows at physiologically elevated levels has also not been investigated. The effects of a 40-min constant NPY infusion (3 pmol kg-1 min-1) at rest and during 130 min of exercise (50% of VO2max) were studied in six healthy subjects and compared with resting and exercising subjects receiving no NPY. Blood samples were drawn from arterial, hepatic and renal vein catheters for the determination of blood flows (indicators: cardiogreen and para-aminohippuric acid [PAH]), NPY, catecholamines, glucose, lactate and glycerol. NPY infusion was accompanied by: (1) significant fractional extraction of NPY-like immunoreactivity (NPY-Li) by splanchnic tissues at rest (58 +/- 5%) and during exercise (53 +/- 6%), while no arterial-venous differences could be detected across the kidney; (2) a reduction in splanchnic and renal blood flows of up to 18 and 13% respectively (P less than 0.01-0.001) at rest without any additional changes during exercise; and (3) metabolic changes as reflected in: (a) a more marked fall in arterial glucose during exercise compared to the reference group (P less than 0.05); (b) a 35% lower splanchnic glucose release (P less than 0.01) during exercise due to diminished glycogenolysis (P less than 0.01); and (c) a lower arterial lactate level (18% P less than 0.05) together with unchanged splanchnic lactate uptake during exercise, suggesting reduced lactate production by extrahepatic tissues. The disappearance of plasma NPY-Li after the infusions was biphasic with two similar half-lives at rest (4 and 39 min) and during exercise (3 and 43 min).

106. Alterations in circulating and cardiovascular tissue content of neuropeptide Y-like immunoreactivity during the development of deoxycorticosterone acetate salt hypertension in the rat

To investigate the modification of plasma and tissue neuropeptide Y-like immunoreactivity (NPY-li) concentrations, in relation to blood pressure and plasma catecholamine levels, during the development of deoxycorticosterone acetate (DOCA)-salt hypertension. Mean arterial pressure (MAP), heart rate, tissue and plasma NPY-li levels, and aortic norepinephrine and epinephrine plasma levels were measured in conscious DOCA-salt hypertensive rats treated for 1, 2 and 3 weeks, and in their respective normotensive controls. Both norepinephrine and NPY-li plasma levels increased significantly in parallel with blood pressure during DOCA-salt treatment, so that MAP was significantly correlated with plasma norepinephrine and NPY-li levels in hypertensive rats. Plasma NPY-li levels were also correlated with norepinephrine levels only in hypertensive rats, but were correlated with epinephrine levels only in normotensive animals. Tissue NPY-li content was lower in the mesenteric artery and heart ventricles after 1-3 weeks of DOCA-salt treatment, but the content in the adrenal gland was not significantly different from that in normotensive rats. In DOCA-salt hypertensive rats, increased plasma NPY-li levels originate primarily from the sympathetic nerves, since those levels were correlated exclusively with circulating norepinephrine levels and they were associated with a reduction in NPY-li content of the heart and mesenteric artery. It is thus possible that the enhanced release of NPY-li from sympathetic nerves could contribute to the rise in blood pressure and to the maintenance of hypertension in this experimental model.

Haemodynamic and humoral responses to repeated hypotensive haemorrhage in conscious sheep

Haemodynamic and humoral responses to two subsequent hypotensive haemorrhages, separated by 3 hours and each followed by retransfusion, were studied in unanaesthetized sheep. Haemorrhage was induced by removal of blood from a jugular vein at a rate of 0.7 ml kg-1 min-1 until the mean systemic arterial pressure suddenly decreased by 35 mmHg or more. In addition to the mean systemic arterial pressure, the cardiac output, the mean pulmonary arterial pressure, the central venous pressure and the pulmonary capillary wedge pressure decreased in response to each haemorrhage. The recovery of the systemic and pulmonary arterial pressure was slower and/or less efficient after the second haemorrhage, due to a less pronounced increase of the vascular resistance. Relative bradycardia, in association with the abrupt fall of the mean systemic arterial pressure, was more apparent during the first haemorrhage. The plasma levels of vasopressin, renin activity and angiotensin II were increased by each blood removal, but the vasopressin response to the second haemorrhage was significantly reduced. The plasma noradrenaline concentration was slightly and transiently elevated only in response to the second haemorrhage. The concentration of neuropeptide Y-like immunoreactivity in plasma was unaffected by both haemorrhages. It is suggested that the reduced and delayed increase in the systemic vascular resistance, accompanied by impaired recovery of the arterial pressure, and the relative absence of 'bleeding bradycardia', during the second haemorrhage, were due to the diminished vasopressin response.