Neuropeptide Y-like Immunoreactivity Levels Research Articles

Alterations in striatal neuropeptide Y system activity of rats with haloperidol-induced behavioral supersensitivity

The study was conducted to determine whether the expression of behavioral supersensitivity induced by haloperidol (HAL) administered once daily (2 mg/kg i.p.) for 14 days is associated with the alterations in activity of neuropeptide Y (NPY) system in the striatum (caudate-putamen) and nucleus accumbens. Dopamine supersensitivity was tested by measurement of locomotor activity and stereotyped behavior after administration of the dopamine D2/D3 receptor agonist quinpirole (1 mg/kg i.p.) on day 1, 3 and 7 after HAL withdrawal. Neuropeptide Y-like immunoreactivity (NPY-LI) was determined in the striatum and nucleus accumbens isolated 6 h after quinpirole injection on day 1, 3 and 7 after the end of HAL treatment. NPY mRNA was quantified in these structures on day 7 after HAL withdrawal. HAL increased spontaneous locomotor activity and prevalence of rearing, grooming and head-down sniffing. At the same time, striatal NPY-LI increased progressively from the reduced level found on day 1 of haloperidol withdrawal. NPY mRNA remained unchanged. In saline-treated rats, quinpirole enhanced locomotion, rearing, and induced intense head-down sniffing and oral activity. These behavioral effects were accompanied by a decrease in striatal NPY-LI. NPY mRNA was slightly increased. HAL treatment altered response to quinpirole, namely it increased locomotion, intensified oral activity and reduced rearing and head-down sniffing. The second and the third quinpirole injection decreased NPY-LI levels. NPY mRNA was unchanged. In the nucleus accumbens, apart from a decrease in NPY-LI on day 1 after the last haloperidol dose, the level of NPY-LI and NPY mRNA in any experimental group did not differ from the control value. The presented results suggest that the alterations in the activity of the striatal but not nucleus accumbens NPY system contribute to adaptive changes induced by long-term haloperidol treatment and may be of significance to the motor hyperactivity induced by intermittent stimulation of postsynaptic dopamine D2 receptors.

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.

Diazepam and buspirone alter neuropeptide Y-like immunoreactivity in rat brain

Neuropeptide Y-like immunoreactivity (NPY-LI) was investigated in naÏve Sprague-Dawley rats subjected to acute, subchronic (7 days) or chronic (21 days) intraperitoneal treatment with diazepam (1 or 3 mg/kg once daily) or buspirone (1.5 or 5 mg/kg twice daily). NPY-LI was determined by radioimmunoassay in the amygdala, nucleus accumbens, hypothalamus and frontal cortex 24 h after the last dose of the drugs. Amygdala NPY-LI decreased after acute diazepam (3 mg/kg) or buspirone (1.5 mg/kg) and increased after subchronic treatment with both doses of diazepam and after chronic buspirone (1.5 mg/kg) treatment. Both diazepam and buspirone given in subchronic and chronic doses decreased NPY-LI levels in the nucleus accumbens. Hypothalamic NPY-LI changed only after chronic treatment: it decreased after diazepam and increased after buspirone (5 mg/kg). NPY-LI content in the frontal cortex decreased after subchronic diazepam (3 mg/kg) treatment and slightly increased after buspirone. The study has shown that both diazepam and buspirone affect NPY-LI levels in rats. These results suggest that the NPY system in the amygdala and nucleus accumbens is implicated in the anxiolytic effects of the drugs studied.

Influence of typical and atypical antipsychotics on neuropeptide Y-like immunoreactivity and NPY mRNA expression in rat striatum

Striatal neuropeptide Y-like immunoreactivity (NPY-LI) levels were investigated in naive rats after acute, subchronic (14 days) or chronic (28 days) intraperitoneal (i.p.) treatment with chlorpromazine (2 or 10 mg/kg), haloperidol (0.5 or 2 mg/kg), (±)sulpiride (50 or 100 mg/kg) or clozapine (10 or 25 mg/kg), and in chronically treated rats after 8-day drug withdrawal. The most pronounced changes in NPY-LI levels were found 24 h after acute chlorpromazine or haloperidol administration (a decrease) and after withdrawal of chlorpromazine, haloperidol or sulpiride (an increase). The effect of clozapine on NPY-LI differed from those of the other antipsychotics: both single doses had no effect, the higher chronic dose increased NPY-LI levels, and its withdrawal resulted in their decrease. No significant alterations were detected in the hybridization signal of NPY mRNA in response to acute or subchronic administration of haloperidol or clozapine. Our results suggest that the effects of antipsychotics are in part mediated by blockade of dopamine D 2-like (D 2/D 3) or serotonin 5HT 2A receptors but not dopamine D 1, D 4 or α 1-adrenergic receptors. The antipsychotic-induced changes in NPY system activity has been discussed in connection with adaptive alterations in the dopamine system.

α-Lipoic acid corrects neuropeptide deficits in diabetic rats via induction of trophic support

This study compared the effects of treatment of diabetic rats with either α-lipoic acid (100 mg/kg/day i.p. 5 days/week) or with recombinant human nerve growth factor (rhNGF; 0.2 mg/kg s.c. 3 days/week) on NGF-like immunoreactivity (NGFLI) and neuropeptide Y-like immunoreactivity (NPYLI) levels in the sciatic nerve and on the release of substance P-like immunoreactivity (SPLI) from the spinal cord in response to electrical stimulation of the dorsal roots in vitro. Diabetic rats showed depletion of NGFLI and NPYLI, together with reduced release of SPLI. Treatment with NGF increased the sciatic nerve NGFLI (to four times that seen in untreated diabetic rats) and normalised stimulus-evoked release of SPLI, but did not affect the sciatic nerve NPYLI. Treatment with α-lipoic acid caused a small non-significant increase in sciatic nerve NGFLI, but normalised both NPYLI levels and stimulus-evoked release of SPLI. These findings indicate that α-lipoic acid can boost neurotrophic support in diabetic rats, with effects beyond those related to NGF.

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.

Chronic parenteral antidepressant treatment in rats: Unaltered levels and processing of neuropeptide Y (NPY) and corticotropin-releasing hormone (CRH)

We have previously reported elevated brain tissue contents of neuropeptide Y-like immunoreactivity (NPY-LI) following 3 weeks of oral treatment with the antidepressants zimelidine and imipramine. Other studies have not reproduced this finding. To eliminate the possibility that this has been due to insufficient treatment duration, dosage, or differences in route of administration or assay specificity, we have administered the selective serotonin reuptake inhibitor citalopram and the preferential noradrenaline reuptake inhibitor desmethylimipramine parenterally for 6 weeks. NPY-LI was assayed using both the assay employed in the original study, and an assay based on a different antiserum which has been extensively examined for cross-reactivity. To exclude the possibility that differential processing rather than altered synthesis rate is responsible for apparent changes in NPY-LI, HPLC analysis of immunoreactive fragment profiles was used. No differences in NPY-LI levels were seen in the brain regions examined, and no differences in HPLC profiles of NPY-LI were present with either drug. We conclude that chronic parenteral administration of antidepressant drugs in naive (non-depressed) animals does not affect the synthesis or processing of NPY. Another neuropeptide implicated in mechanisms of depression, corticotropin-releasing hormone (CRH) was also found to be unaffected by a similar analysis.

Tetrodotoxin-sensitive release of adrenaline, noradrenaline and neuropeptide Y-like immunoreactivity in the pithed guinea-pig in the absence of electrical preganglionic nerve stimulation

The effect of tetrodotoxin (TTX) on plasma noradrenaline (NA), adrenaline (A) and neuropeptide Y-like immunoreactivity (NPY-LI) levels was evaluated in the pithed guinea pig, in the absence of electrical stimulation and following preganglionic nerve stimulation (PNS). Blood samples for determination of NA, A and NPY-LI were collected 5 min before and 5 min after injection of saline (control group, n = 6) or TTX (13 μg/kg, i.v., TTX-treated group, n = 8), respectively. In both groups, blood samples were collected 20 s and 40 s after initiation of PNS. In the absence of electrical stimulation, TTX reduced the plasma NA level by 66%, NPY-LI level by 42%, whereas the plasma A level was not significantly altered by the neurotoxin. In the control group, PNS elicited a 27-fold increase of plasma NA, a 60-fold increase of plasma A and enhanced the NPY-LI levels by 13%. Pretreatment with TTX completely blocked this release of sympathetic transmitters. The present results suggest that a certain degree of spontaneous nerve activity is present in the pithed animal model, also during baseline conditions, since TTX significantly reduced NA and NPY-LI in the absence of electrical stimulation. This spontaneous nerve activity is probably a consequence of local mechanical activity of the pithing rod capable of eliciting action potentials at the preganglionic level of the sympathetic nerve terminals.

Effects of peripheral nerve injuries and tissue inflammation on the levels of neuropeptide Y-like immunoreactivity in rat primary afferent neurons

Changes in neuropeptide Y-like immunoreactivity (NPYir) in the rat L 4 and L 5 spinal cord and dorsal root ganglia (DRG) were examined after different sciatic nerve injuries (transection, loose ligation, and crush) and a localized, painful inflammation of the hind paw. Inflammation had no effect on NPYir. All the nerve injuries produced comparable increases in NPYir in ipsilateral laminae III–V axons and varicosities, and induction of NPYir in many DRG cells. Most NPYir DRG cells were medium to large (mean diameters: 40–45 μm); less than 2% of the cells had diameters of 25 μm or less. We conclude that the nerve injury-evoked increase in NPYir occurs mostly in the somata and intraspinal arbors of low-threshold mechanoreceptors; very few, if any, C-fiber afferents are involved. Nerve injury, rather than a painful condition, appears to be the stimulus for the induction of NPYir synthesis.

Effect of serotonergic agents on regional concentrations of somatostatin- and neuropeptide Y-like immunoreactivities in rat brain

A possible role for neuropeptides in affective disorders is suggested by many investigators. Somatostatin-like immunoreactivity (SS-LI) and neuropeptide Y-like immunoreactivity (NPY-LI) concentrations are demonstrated to be reduced in cerebrospinal fluid from depressed patients. We have shown that long-term treatment with serotonin uptake inhibitors, clomipramine and zimelidine, reduce brain SS-LI concentrations in the rat. We have studied the effect of serotonergic agents on regional brain SS-LI and NPY-LI concentrations in rats. Long-term treatment with 5-hydroxytryptamine (5-HTP), a serotonin precursor, caused reductions in SS- and NPY-LI levels in the hypothalamus. SS-and NPY-LI concentrations in the brain were markedly elevated by treatment with p-chlorophenylalanine, a serotonin synthesis inhibitor. Intracerebroventricular administration of 5,7-dihydroxytryptamine, a serotonin neurotoxin, resulted in elevations of both peptides in the brain. These results suggest a inhibitory role for the serotonergic system in the brain in the regulation of SS and NPY.

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.

Characterization of phencyclidine-induced effects on neuropeptide Y systems in the rat caudate-putamen

Multiple administrations of the psychotominetic drug, phencyclidine-HC1 (PCP), decreased striatal neuropeptide Y-like immunoreactivity (NPY-LI) levels in a dose-dependent manner. Single or multiple PCP administrations decreased striatal NPY levels after 10–12 h; levels returned to control 24 h after a single dose or 58 h after multiple doses. In contrast, no significant changes were seen in nigral NPY levels with either acute or multiple-dose PCP treatments. The role of monoamine, σ or opioid receptors in PCP-induced striatal NPY changes was evaluated. When administered alone, the α 1-adrenergic antagonist, prazosin, the σ antagonist, BMY 14802, and the dopamine D 2 antagonist, sulpiride decreased striatal NPY levels; however, only prazosin and the dopamine D 1 antagonist, SCH 23390, significantly attenuated PCP-induced changes. Administration of the γ-aminobutyric acid transaminase (GABA-T) inhibitors, amino-oxyacetic acid (AOAA) or γ-vinyl-GABA (GVG, vigabatrin, MDL 71,754) alone had no effect on striatal NPY-LI levels while administration of these indirect GABA agonists prior to or concurrently with PCP treatment completely blocked PCP-induced changes in striatal NPY-LI levels. The effect of the non-competitive N- methyl- d- aspartate (NMDA) receptor antagonist, MK-801, on striatal NPY-LI content resembled that of PCP and was also blocked by the two indirect GABA agonists. These data suggest that NPY systems are modulated by glutamatergic activity (specifically by the NMDA receptor) and that the interaction between these two transmitter systems is mediated by GABAergic mechanisms.

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.

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.

Characterization of neuropeptide Y-like immunoreactivity in vertebrate retina

We have determined the endogenous levels of neuropeptide Y-like immunoreactivity (NPY-LI) in retinal extracts from pigs, cats, rabbits, chickens, and frogs by radioimmunoassay (RIA). The NPY-LI levels varied among the species. The highest concentration was found in frog retina, where seasonal variations were seen, 861 ± 31 pmol g −1 wet weight in the autumn and 334 ± 26 pmol g −1 wet weight in the spring. Lower levels were demonstrated in chicken and pig retina, 4·1 ± 0·4 and 3·6 ± 0·3 pmol g −1 wet weight. respectively. The lowest concentration was demonstrated in rabbit retina, 2·0 ± 0·3 pmol g −1 wet weight. (All values are expressed as mean ± s.e.m.) The NPY-LI in pig, rabbit, chicken and frog retina was characterized by high-performance liquid chromatography (HPLC). The main part of the extracted NPY-LI had an elution volume close to that to the porcine NPY. We have also analysed the evoked release of endogenous NPY from frog retina, induced either with light flashes (3 Hz, 300 lx), or with potassium depolarization of the neurons (40 m m). Light flashes and potassium induced an increased release of NPY-LI of 61 and 77%, respectively. NPY-LI in the efflux had the same HPLC retention time as that extracted directly from the retina.

Effect of captopril on plasma levels of neuropeptide Y (NPY)-like immunoreactivity in the pithed guinea pig

The effect of exogenous angiotensin II (A II) and the angiotensin convertinng enzyme (ACE)-inhibitor captopril on plasma levels of neuropeptide Y-like immunoreactivity (NPY-LI) has been studied in the pithed guinea pig. Four periods of pre-ganglionic nerve stimulation (PNS, 8Hz for 30s with 20 min intervals) were applied and the increases of mean arterial blood pressure (ΔBP), heart rate (ΔHR) and plasma NPY-LI (ΔNPY-LI) in response to PNS were analysed in non-pre-treated and captopril pre-treated animals. Captopril (5 mg × kg −1 i.v.) reduced basal blood pressure and ΔBP by 20% and 11%, respectively. Infusion of A II (0.5 μg × kg −1 = min −1 i.v.) caused a significant increase in basal and PNS-induced maximal blood pressure response but reduced ΔBP in captopril and non-pre-treated animals by 40% and 16%, respectively. A II elicited a long-lasting increase of basal heart rate by 12% but reduced ΔHR by 36% in non-pre-treated animals. However, neither captopril alone nor A II infusion to captopril pre-treated animals significantly changed heart-rate values. The effects of exogenous A II on the cardiovascular responses were abolished by the A II-antagonist saralasin (a bolus injection, 40 μg × kg −1 i.v. followed by an infusion, 30 μg × kg −1 × min −1), which per se had no significant effect. Captopril pre-treatment reduced basal plasma NPY-LI levels by 38% and ΔNPY-LI by 46% in response to PNS 1. However, neither in non-pre-treated nor in captopril pre-treated animals did infusion of A II significantly change the plasma NPY-LI level. It is concluded that ACE-inhibition reduces basal plasma NPY-LI level as well as nerve stimulation-evoked increase of plasma NPY-LI in the pithed guinea pig.

Increased plasma levels of neuropeptide Y-like immunoreactivity and catecholamines in severe hypertension remain after treatment to normotension in man

Circulating levels of neuropeptide Y (NPY)-like immunoreactivity (-LI), adrenaline and noradrenaline (NA) were analysed in 17 patients admitted to the emergency ward due to severe hypertension; blood pressure mean 204/127 mmHg. The levels of NPY-LI and NA were significantly higher ( P < 0.001) in the hypertensives as compared to a normotensive control group. HPLC analysis revealed that the plasma contained besides NPY-LI also several NPY-LI fragments of low hydrophobicity. Following 2 to 3 weeks treatment the blood pressure had decreased to a mean of 150/89 mmHg. However, circulating levels of NPY-LI ( P < 0.001) and NA ( P < 0.01) were still significantly higher than in controls in spite of the marked reduction in blood pressure. Simultaneous measurements of adrenaline did not reveal any significant changes and these values did not differ compared with those in the normotensive subjects. The findings suggest that peripheral markers of the sympathetic system (NPY-LI and NA) in severe hypertension is not directly related to the blood pressure level.

Elevation of plasma neuropeptide Y‐like immunoreactivity and noradrenaline during myocardial ischaemia in man

Plasma levels of neuropeptide Y-like immunoreactivity (NPY-LI) and noradrenaline were studied for 25 h in 22 patients with acute ischaemic heart disease. On admission, NPY-LI levels were above normal in 16 patients, and 20 patients had increased noradrenaline levels. The initial plasma NPY-LI did not differ between patients with acute myocardial infarction (AMI) and angina pectoris. Initial plasma noradrenaline levels were higher in patients with AMI than in those with angina pectoris. Plasma levels of noradrenaline remained elevated in AMI patients, but decreased towards normal values in patients with angina pectoris. Levels of NPY-LI returned to normal within 25 h in all patients. Tachycardia and left ventricular failure were related to high NPY-LI and noradrenaline levels. A positive correlation was found between noradrenaline and NPY-LI in plasma. It is suggested that neuropeptide Y (NPY), an endogenous vasoconstrictor peptide, should be considered as one of the mediators involved in the cardiovascular response to sympathetic activation induced by myocardial ischaemia.

Corelease of neuropeptide Y like immunoreactivity with catecholamines from the adrenal gland during splanchnic nerve stimulation in anesthetized dogs

The release of neuropeptide Y like immunoreactivity (NPY-li) from the adrenal gland was studied in relation to the secretion of catecholamines (CA: NE, norepinephrine; E, epinephrine) during the left splanchnic nerve stimulation in thiopental-chloralose anesthetized dogs (n = 16). Plasma concentrations of NE, E, and NPY-li were determined in the left adrenal venous and aortic blood. Adrenal outputs of NPY-li, NE, and E were 2.4 +/- 0.4, 1.4 +/- 0.2, and 7.3 +/- 1.7 ng/min, under basal conditions, respectively. These values increased significantly (p less than 0.05; n = 8) in response to a continuous stepwise stimulation at frequencies of 1, 3, and 10 Hz given at 3-min intervals during 9 min, reaching a maximum output of 4.6 +/- 0.9 (NPY-li), 240.2 +/- 50.2 (NE), and 1412.5 +/- 309.7 ng/min (E) at a frequency of 10 Hz. Burst electrical stimulation at 40 Hz for 1 s at 10-s intervals for a period of 10 min produced similar increases (p less than 0.05) in the release of NPY-li (4.8 +/- 1.0 ng/min, n = 8), NE (283.5 +/- 144.3 ng/min, n = 8), and E (1133.5 +/- 430.6 ng/min, n = 8). Adrenal NPY-li output was significantly correlated with adrenal NE output (r = 0.606; n = 24; p less than 0.05) and adrenal E output (r = 0.640; n = 24; p less than 0.05) in dogs receiving the burst stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Congestive heart failure: involvement of perivascular peptides reflecting activity in sympathetic, parasympathetic and afferent fibres

In controls and in patients suffering from congestive heart failure (CHF) the circulating levels of catecholamines, neuropeptide Y-like immunoreactivity (NPY-LI), vasoactive intestinal peptide-LI (VIP-LI), substance P-LI (SP-LI) and calcitonin generated peptide-LI (CGRP-LI) markers of sympathetic, parasympathetic and sensory nervous systems, respectively, have been examined. There was a significant rise in the levels of noradrenaline, NPY-LI and SP-LI already in moderate CHF (New York Heart Association Stage I and II). In patients with severe CHF (NYHA Stage III and IV) the circulating levels of noradrenaline, adrenaline, NPY-LI and SP-LI were significantly increased. CGRP-LI was not altered, despite the fact that this peptide co-exists in many tissues with SP. There was no change in VIP-LI. The pathophysiological significance of this pattern of reaction of circulating catecholamines and neuropeptides is unclear; however, the rise in SP-LI may be a reaction to counterbalance the vasoconstrictive effects of the activation of the sympatho-adrenal system.