Neuropeptide Y: presence in perivascular noradrenergic neurons and vasoconstrictor effects on skeletal muscle blood vessels in experimental animals and man

The presence of neuropeptide Y (NPY)-like immunoreactivity (-LI) in sympathetic perivascular nerves and the functional effects of NPY and noradrenaline (NA) on vascular tone were studied in skeletal muscle of various species. A dense network of NPY-LI was found around arteries and arterioles but not venules in the gluteus maximus muscle of man, gracilis muscle of dog, tenuissimus muscle of rabbit and quadriceps muscle of cat, rat, guinea pig and pig. The distribution of NPY-immunoreactive (-IR) nerves was closely correlated to the presence of tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH)-positive fibers, two markers for noradrenergic neurons. Double-staining experiments revealed that NPY- and TH-IR as well as NPY- and DBH-IR nerve fibers around arteries and arterioles were identical. The veins and venules, however, lacked or had a very sparse innervation of NPY-, TH- and DBH-positive fibers. The NPY- and TH-IR nerves in quadriceps muscle of the guinea pig were absent after treatment with 6-hydroxydopamine. Lumbosacral sympathetic ganglia from the same species contained many NPY-positive cells which were also TH- and DBH-IR. NPY-LI was also detected by radioimmunoassay in extracts of skeletal muscle from guinea pig, rabbit, dog, pig and man as well as of lumbosacral sympathetic ganglia. The content of NPY-LI in skeletal muscle was relatively low (0.1-0.4 pmol/g), whereas lumbosacral sympathetic ganglia had a much higher content (48-88 pmol/g). NPY (10(-7) M) contracted arterioles in the tenuissimus muscle of the rabbit to a similar extent (by 65%) as NA (10(-6) M), as studied by intravital microscopy in vivo. NPY had no effect on the corresponding venules while NA caused a slight contraction of these vessels. In vitro studies of small human skeletal muscle arteries and veins revealed that NPY was more potent than NA in contracting the arteries, and the highest concentration of NPY (5 x 10(-7) M) caused a contraction of a similar magnitude as NA 10(-5) M. NA contracted veins from human skeletal muscle, while NPY had only small effects. It is suggested that NPY, together with NA, could be of importance for sympathetic control of skeletal muscle blood flow.     

Detection of neuropeptide Y-like immunoreactivity and messenger RNA in rat platelets: the effects of vinblastine, reserpine, and dexamethasone on NPY expression in blood cells.

Rat plasma contains high basal levels (220 pmol/liter) of neuropeptide Y (NPY)-like immunoreactivity (LI) compared to pig (30 pmol/liter) and man (25 pmol/liter). The platelet-enriched fraction (PEF), obtained from rat blood contained 10,061 pmol/g NPY-LI. However, in human and pig blood, the PEF contained very low levels of NPY-LI. Gradient centrifugation of rat blood showed the highest concentration of NPY-LI (10.8 +/- 0.4 pmol/g) in the platelet fraction. The mononuclear cell fraction contained 1.64 +/- 0.16 pmol/g, whereas only 0.56 +/- 0.06 pmol/g of NPY-LI was found in the red blood cell/polymorphonuclear cell fraction. Characterization of NPY-LI in rat plasma and platelets by high-pressure liquid chromatography showed one predominating peak which coeluted with synthetic NPY (1-36) as well as three minor peaks, one of which coeluted with oxidized NPY. Analysis of NPY messenger RNA (mRNA) in bone marrow of the rat revealed a 0.79-kb-long NPY mRNA. This size is intermediate to the 0.82-kb NPY mRNA in brain and the 0.76-kb NPY mRNA in spleen. The highest level of NPY mRNA in rat blood was found in the mononuclear cell fraction but NPY mRNA was also detected in the platelet fraction. No NPY mRNA was detected in bone marrow or blood from pig and rabbit or from human blood or bone marrow. Forty-eight hours after treatment of rats with vinblastine the content of NPY mRNA and NPY-LI in rat blood was decreased, while the level of NPY-LI in bone marrow was markedly enhanced. Reserpine treatment caused an increase in NPY mRNA content in bone marrow and spleen. After administration of dexamethasone the level of NPY mRNA increased in both spleen and peripheral blood cells with increased NPY-LI content in the spleen. It is concluded that in addition to megakaryocytes in spleen and bone marrow, platelets and possibly also lymphocytes/monocytes in peripheral blood of the rat contain NPY mRNA and peptide. The expression of NPY mRNA in bone marrow, spleen, and blood is influenced by vinblastine, reserpine, and dexamethasone.     

Vasoconstrictor effects in vivo and plasma disappearance rate of neuropeptide Y in man

Vascular effects of neuropeptide Y (NPY) and noradrenaline (NA) were studied in six human volunteers. Systemic infusion of human NPY for 40 min (5 pmol X kg-1 X min-1) increased arterial plasma NPY-like immunoreactivity (NPY-LI) from 12 +/- 2 to 356 +/- 30 pM. This concentration caused no systemic cardiovascular effects. The disappearance curve for NPY-LI was biphasic; the slopes of the two phases corresponding to half lives of 4.1 +/- 0.4 and 20 +/- 2 min respectively. Close i.a. infusion of human NPY in the forearm caused a slowly developing and dose dependent decrease in forearm blood flow (FBF) and increase in venous tone with maximal values of 44 +/- 6 and 235 +/- 81% of control respectively at 5 nmol X min-1. The corresponding values for NA (5 nmol X min-1) were 21 +/- 9 and 489 +/- 78% of control. A threshold concentration for a decrease in FBF was obtained at a plasma NPY-LI of 3.7 +/- 0.6 nM. The decrease in FBF caused by NPY was maintained for a much longer period compared to that of NA.     

Neuropeptide Y (NPY) and the pig heart: release and coronary vasoconstrictor effects

The effects of electrical stimulation of the stellate ganglia on the arterio-venous concentration differences of neuropeptide Y (NPY)-like immunoreactivity (LI) over the pig heart were studied in vivo in relation to changes in heart rate and left ventricular pressure. Furthermore, the effects of NPY on coronary vascular tone were analysed in vivo and in vitro. Stellate ganglion stimulation at a high frequency (10 Hz) caused a clear-cut, long lasting increase in plasma levels of NPY-LI in the coronary sinus compared to the aorta, suggesting release of this peptide from sympathetic terminals within the heart. The stimulation-evoked overflow of NPY-LI from the heart was enhanced about 3-fold by alpha-adrenoceptor blockade using phenoxybenzamine, suggesting that NPY release is under prejunctional inhibitory control by noradrenaline (NA). Combined alpha- and beta-adrenoceptor blockade abolished most of the positive inotropic response of the heart upon stellate ganglion stimulation, while a considerable positive chronotropic effect remained. After guanethidine treatment, stellate ganglion stimulation still produced a small positive inotropic and chronotropic effect on the heart. The stimulation evoked NPY overflow was markedly reduced by guanethidine indicating an origin from sympathetic nerve terminals. Injection of NPY into the constantly perfused left anterior descending artery in vivo caused a long lasting, adrenoceptor antagonist resistant increase in perfusion pressure, suggesting coronary vasoconstriction. NPY contracted coronary arteries in vitro via a nifedipine-sensitive mechanism. NA dilated coronary vessels both in vivo and in vitro via beta-adrenoceptor activation. It is concluded that sympathetic nerve stimulation increases overflow of NPY-LI from the heart suggesting release from cardiac nerves in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)     

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 less than 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 less than 0.001) and NA (P less than 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.     

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.     

Stress-induced changes of circulating neuropeptide Y in the rat: comparison with catecholamines

Circulating concentrations of neuropeptide Y-like immunoreactivity (NPY), noradrenaline (NA) and adrenaline (AD) were measured in conscious, chronically catheterized rats submitted to various stress protocols. Basal plasma levels of NPY, NA and AD (194 +/- 52 fmol/ml, 0.90 +/- 0.11 pmol/ml and 0.52 +/- 0.07 pmol/ml) were increased by handling (+132%, +76% and +629%, respectively) and rose further during electric shock treatment. Adrenalectomy resulted in the complete disappearance of circulating adrenaline but did not alter either control or stress values of noradrenaline. In comparison circulating levels of NPY were reduced, but not significantly in adrenalectomized animals. Insulin stress induced a large increase in plasma AD levels and cold stress induced an increase in plasma NA levels, without any parallel change in NPY concentrations. These results demonstrate that NPY, which is colocalized with catecholamines in the peripheral nervous systems, is also released during stress responses and that its release parallels more closely changes in circulating NA than AD. Furthermore, stress-induced changes in circulating NPY-like immunoreactivity do not originate from the adrenal gland but mainly from the peripheral nervous system, and the release of NPY is dependent upon the nature of the stimulus.     

Neuropeptide Y Y1 receptor mediated mesenteric vasoconstriction in the pig in vivo

The object of the present study was to investigate the effects of the sympathetic cotransmitter neuropeptide Y (NPY), and the closely related gut hormone peptide YY (PYY), on splanchnic blood flow regulation in the anaesthetized pig in vivo. Systemic injections of NPY, PYY and the NPY Y(1) receptor agonist [Leu(31)Pro(34)]NPY (470 pmol kg(-1) each) evoked pressor and mesenteric vasoconstrictor responses that were largely abolished by the selective NPY Y(1) receptor antagonist H 409/22 (60 nmol kg(-1) min(-1)). In contrast, the NPY Y(2) receptor agonist N-acetyl[Leu(28)Leu(31)]NPY(24-36) (1.1 nmol kg(-1)), a dose of which potently evoked splenic NPY Y(2) receptor mediated (not affected by H 409/22) vasoconstriction, did not evoke any mesenteric vascular response. Mesenteric vascular responses to angiotensin II (10 pmol kg(-1)), alpha,beta-methylene ATP (10 nmol kg(-1)) and the alpha(1)-adrenoceptor agonist phenylephrine (15 nmol kg(-1)), were not inhibited by H 409/22. It is concluded that NPY and PYY evokes porcine mesenteric vasoconstriction mediated by the NPY Y(1) receptor subtype, as demonstrated by selective and specific inhibition exerted by the NPY Y(1) receptor antagonist H 409/22, in vivo.     

Roles of neuropeptide Y and noradrenaline in sympathetic neurotransmission to the thoracic vena cava and aorta of guinea-pigs.

The roles of neuropeptide Y (NPY) and noradrenaline (NA) in sympathetic neurotransmission to large arteries and veins were studied in vitro using the thoracic portions of the aorta and inferior vena cava from guinea-pigs. Both vessels are densely innervated by axons containing NA and NPY. Repetitive transmural stimulation at 2-30 Hz produced contractions of the aorta, which were abolished by prazosin. NPY did not have significant postsynaptic or presynaptic effects on vascular tone of the aorta. Transmural stimulation of the vena cava produced long-lasting contractions which were enhanced by alpha- and beta-adrenoceptor antagonists, and were blocked by guanethidine. Precontracted venae cavae responded to sympathetic stimulation with beta-adrenoceptor-mediated relaxation, followed by contraction. alpha-Adrenoceptor blockade delayed the onset of neurogenic contractions. NPY was a potent contractile agent of the vena cava (EC50 approximately 1.5 x 10(-8) M). A high concentration (3 x 10(-6) M) of NPY, or the specific NPY Y1 receptor agonist, [Leu31, Pro34]NPY, caused parallel, and reversible, desensitization of contractions produced by sympathetic nerve stimulation, and by low concentrations of exogenous NPY. This provides good evidence that NPY is the mediator of the non-adrenergic sympathetic contractions of the vena cava. Furthermore, these results demonstrate that differential location or coupling of postsynaptic receptors for NA and NPY in the aorta and vena cava, leads to differential participation by these substances in sympathetic vasomotor responses. This is likely to be related to the different functions of these two parts of the systemic circulation.     

Neuropeptide Y stimulates DNA synthesis in human vascular smooth muscle cells through neuropeptide Y Y1 receptors

We investigated the mitogenic effect, measured as [3H]thymidine incorporation, of neuropeptide Y (NPY) on smooth muscle cells (SMCs) from human subcutaneous arteries (diameter: 0.4 mm). NPY stimulated DNA synthesis in a concentration-dependent manner, Emax 32 +/- 5% relative to control. The effect was potently antagonised by the NPY Y1 receptor antagonist BIBP3226 ((R)-N2-(diphenylacetyl)-N-[(4-hydroxy-phenyl)methyl]-D-arginine-a mide), indicating the effect to be mediated via the NPY Y1 receptor. Noradrenaline (NA) also induced mitogenesis, Emax 35 +/- 10% relative to control. When added together, NPY and NA potentiated the [3H]thymidine incorporation, Emax 109 +/- 38% relative to control. Also, this effect seems to be mediated by the NPY Y1 receptor, since BIBP3226 blocked the effect (44 +/- 9% relative to control). The mitogenic effect of NPY and NA, two important transmitters of the sympathetic nervous system, might have clinical consequences on conditions with elevated sympathetic nerve activity.     

自发性高血压大鼠血管α1肾上腺素受体亚型的改变

本工作在离体与整体条件下比较易卒中型自发性高血压(SHRSP)大鼠与WKY大鼠血管中α_1受体的两种亚型。在离体灌流的主动脉、肾动脉与肠系膜动脉,50μmol/L氯甲基可乐定(CEC)预温育30min可使α_1受体激动时引起的最大收缩张力在SHRSP与WKY大鼠分别降为对照时的31.4±8.3％与35.2±2.9％,68.4±8.2％与80.1±7.3％,68.4±6.3％与55.4±7.0％,两者间均无显著性差别。但10μmol/L硝苯吡啶对α_1受体收缩效应的阻断作用则在SHRSP大鼠大大超过WKY大鼠,最大收缩张力分别降为对照时的3.1±1.5％与56.5±4.8％(P<0.01),9.0±4.1％与23.6±3.5％(P<0.05),5.9±2.5％与28.0±0.8％(P<0.01)。整体动物实验也显示硝苯吡啶的降血压作用及对苯肾上腺素升血压效应的阻断作用在SHRSP大鼠都较WKY大鼠显著增强。离体主动脉a_1受体激动时的快速相与持续相收缩均主要由α_(1B)亚型激动引起,硝苯吡啶对快速相收缩的阻断作用在SHRSP与WKY大鼠无显著性差别,但对持续相收缩的阻断作用则在SHRSP大鼠显著强于WKY大鼠。上述结果提示SHRSP大鼠血管α_1受体两种亚型的分布没有显著改变,但α_(1B)受体激动时继发性细胞外Ca~(2+)进入的途径由非双氢吡啶敏感性钙通道转变为双氢吡啶敏感性钙通道。     

Significant depletion of NPY in the innervation of the rat mesenteric, renal arteries and kidneys in experimentally (aorta coarctation) induced hypertension

The distribution and concentrations of neuropeptide Y (NPY) in kidneys, renal arteries, heart, aorta, mesenteric artery and adrenal glands from aorta-ligated hypertensive rats were studied by immunocytochemistry and radioimmunoassay. Immunocytochemistry showed that in the hypertensive animals NPY-immunoreactive fibres were decreased in both kidney and renal artery, above and below the ligation, and in mesenteric arteries. The depletion of NPY-containing nerves in the kidney was more pronounced around the juxtaglomerular apparatus than in other areas of the organ. By radioimmunoassay, the concentrations of NPY immunoreactivity were significantly lower in the hypertensive animals when compared with the controls, (kidney: hypertensive 1.0 +/- 0.1; controls 2.0 +/- 0.2 pmol/g, mean +/- SEM; p less than 0.05 renal artery: hypertensive 5.0 +/- 0.8; controls 12.1 +/- 2.0; p less than 0.05 and mesenteric artery: hypertensive 8.6 +/- 1.9; 17.6 +/- 3.0; p less than 0.01). While there were no statistically significant changes in the levels of NPY immunoreactivity in the other areas studied, there was a general trend for the level to fall in the renal artery below the ligation (hypertensive 10.6 +/- 1.5; control 15.3 +/- 2.4; p greater than 0.05). It is of interest that changes were observed in the vasoconstrictor peptide NPY in this commonly used model of hypertension.     

Neuropeptide Y and peptide YY mediate nonadrenergic vasoconstriction and modulate sympathetic responses in rats

The modulation of cardiovascular sympathetic responses by neuropeptide Y (NPY) and peptide YY (PYY) was assessed in vivo, in pithed rats. Both peptides (0.02-2 nmol/kg) caused similar dose-dependent pressor responses, resistant to adrenergic blockade but antagonized by the calcium channel blocker, nifedipine. Only NPY, at the lowest dose, slightly accelerated heart rate (by 10 +/- 4 beats/min). At the pressor dose (0.6 nmol/kg) but not subpressor dose (0.2 nmol/kg), the increase in blood pressure induced by stimulation of the sympathetic outflow (ST: 0.3 Hz, 50 V, 1 min) was attenuated by PYY (by 40%), whereas ST-evoked tachycardia was reduced by NPY (by 35%). Neither NPY- nor PYY-pretreatment affected ST-induced increments in plasma norepinephrine (NE) and epinephrine concentrations. In addition, regional hemodynamic effects of NPY were studied in conscious rats instrumented with Doppler flow probes. The hypertension caused by NPY was attended by reflex bradycardia and marked rise in peripheral vascular resistance in renal (+ 233 +/- 59%), superior mesenteric (+ 183 +/- 65%) and hindquarter (+ 65 +/- 10%) circulation. The pattern of hemodynamic responses of NPY was similar to that of NE but, unlike the latter, persisted after adrenergic blockade.     

Neuropeptide Y- and somatostatin-like immunoreactivities in ganglioneuroma, ganglioneuroblastoma and neuroblastoma

Neuropeptide Y (NPY)- and somatostatin (SS)-like immunoreactivities (LI) were investigated in tumor tissues of one ganglioneuroma (GN), 3 ganglioneuroblastomas (GNB) and one neuroblastoma (NB) by radioimmunoassay. NPY-LI was detected from all 5 tumor tissues (16.4-1247 pmol/g wet tissue). Sephadex G-50 column chromatography and reverse phase high performance liquid chromatography (HPLC) revealed that most of the NPY-LI in tumor extracts was eluted in an identical position to synthetic human NPY except one GNB (case 2). In this case, most of the NPY-LI was eluted in a higher molecular weight region than synthetic human NPY in Sephadex G-50 column chromatography and in a more hydrophobic position in HPLC. SS-LI was detected from 4 tumor extracts except one GNB (case 2) (21.3-787 pmol/g wet tissue). Sephadex G-25 column chromatography and reverse phase HPLC revealed that SS-LI in tumor extracts was eluted just after the void volume and then in the same positions as SS-28 and SS-14. These results suggest that NPY, SS-14 and SS-28 exist in tumor tissues of GN, GNB and NB, and most of the NPY-LI in one GNB was a higher molecular and more hydrophobic form of NPY-LI.     

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.     

Innervation of human omental arteries and veins and vasomotor response to noradrenaline, neuropeptide Y, substance P and vasoactive intestinal peptide

Human omental arteries and veins are supplied with nerve fibers containing noradrenaline (NA) and neuropeptide Y (NPY); these two agents probably co-exist in perivascular sympathetic nerve fibers. Substance P (SP)- or vasoactive intestinal peptide (VIP)-containing fibers could not be detected. In studies on isolated omental vessels NA produced constriction. The results of blockade experiments suggest that human omental arteries are equipped predominantly with alpha 1-adrenoceptors and omental veins with a mixture of alpha 1- and alpha 2-adrenoceptors. NPY at a concentration of 10(-7) M or higher had a weak contractile effect on veins and virtually no effect on arteries. NPY at a concentration of 3 X 10(-8) M shifted the NA concentration response curve to the left in arteries (pD2 = 5.8 for NA versus 6.6. for NA in the presence of NPY; P less than 0.001) but not in veins. Both SP and VIP relaxed arteries precontracted with NA or prostaglandin F2 alpha (PGF2 alpha). The potency of SP as a relaxant agent was similar in arteries and veins; the effect of VIP was elicited at lower concentrations in veins than in arteries.     

Neuropeptide Y is a vasoconstrictor in human nasal mucosa.

Neuropeptide Y (NPY) is a neurotransmitter in sympathetic nerve fibers in human nasal mucosa. Like norepinephrine, NPY acts as a vasoconstrictor. An established method of nasal provocation was used to determine the effects of topically applied NPY on nasal resistance to airflow measured by anterior rhinomanometry, the protein content of nasal secretions, and the protein content of bradykinin-induced secretions. NPY (2.3 nmol) reduced the resistance to inspiratory airflow by 57 +/- 18% (P < 0.001) in 10 normal subjects and by 50 +/- 17% (P < 0.05) in 12 subjects with perennial rhinitis. In nasal provocations, NPY in doses of 0.1-10 nmol had no effect on vascular (albumin), glandular (lysozyme, glycoconjugate), or total proteins present in lavaged nasal secretions. Because the vasoconstrictor properties of NPY may only be apparent in the presence of increased vascular permeability and albumin exudation, bradykinin (BK) nasal provocation was performed. BK (500 nmol) significantly increase total protein (10- to 20-fold), albumin (10- to 30-fold), and glycoconjugate (2- to 5-fold) in lavage fluid. NPY (2.3 nmol) reduced BK-induced total protein by 59 +/- 15% (P < 0.05) and albumin by 63 +/- 17% (P < 0.02) but had no significant effect on glandular secretion. Therefore exogenous administration of NPY to the human nasal mucosa reduced nasal airflow resistance and albumin exudation without affecting submucosal gland secretion. NPY agonists may be useful for the treatment of mucosal diseases characterized by vasodilation, vascular permeability, and plasma exudation.     

Increases of neuropeptide Y-like immunoreactivity in plasma during insulin-induced hypoglycemia in man

Neuropeptide Y-like immunoreactivity (NPY-LI) in plasma during insulin-induced hypoglycemia was measured in 4 healthy male volunteers. Plasma NPY-LI increased from 167 +/- 11 pg/ml to 247 +/- 25 pg/ml 30 min after the administration of insulin (0.1 U/kg body weight IV), reached the maximum (296 +/- 6 pg/ml) 45 min after the insulin, and then decreased. These results suggest that NPY is released into the systemic circulation during insulin-induced hypoglycemia in man.     

Neuropeptide Y and catecholamine release in the piglet during hypoxia: enhancement by theophylline.

Sympathoadrenal activity was studied in 13 young piglets during hypoxia. The piglets were anaesthetized with chloralose/urethane, tracheostomized, paralyzed with gallamine and artificially ventilated. A femoral artery catheter was inserted and used for blood sampling. The piglets were challenged with 6 min of 6% CO2, 10 min of 12% O2 and 6 min of 6% O2 before and after theophylline (an adenosine receptor antagonist) treatment 20 mg/kg (n = 9) or saline (n = 4). Plasma samples were obtained before, during and after each hypercapnic or hypoxic period and analysed for their content of noradrenaline, adrenaline and neuropeptide Y. Hypercapnia with 6% CO2 and moderate hypoxia with 12% O2 did not lead to any significant increase of either noradrenaline (NA), adrenaline (A) or neuropeptide Y (NPY). However, severe hypoxia with 6% O2 increased the NA level from 30 to 66 nmol/l; the A level from 1 to 28 nmol/l and NPY from 140 to 213 pmol/l. After treatment with theophylline the baseline NA increased from 27 to 40 nmol/l, A rom 1.5 to 4.0 and NPY concentration from 65 to 171 pmol/l. Theophylline moderately enhanced the release of NPY, NA and A during the 12% O2 challenge. However, during the severe hypoxia (6%), the increase of NA (from 49 to 333 nmol/l), A (from 8 to 214 nmol/l) and NPY (from 184 to 385 pmol/l) showed considerably enhancement after the theophylline treatment. The results obtained before and after saline were similar showing that the duration of the experiments per se did not change the baseline levels or the effect of the challenges on NA, A or NPY levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Innervation of the large arteries and heart of the toad (Bufo marinus) by adrenergic and peptide-containing neurons

Summary The innervation of the major arteries and heart of the toad (Bufo marinus) was examined by use of glyoxylic acid-induced catecholamine fluorescence and peptide immunohistochemistry. All arteries possessed a moderate to dense plexus of adrenergic axons, which also showed neuropeptide Y-like immunoreactivity (NPY-LI). Some adrenergic axons in the intracardiac vagal trunks showed NPY-LI, but the varicose adrenergic axons innervating the cardiac muscle of the atria and ventricle, and the coronary blood vessels did not display NPY-LI. About half of the nerve cell bodies in the anterior sympathetic chain ganglia with dopamine--hydroxylase-LI (DBH-LI) also contained NPY-LI. The nerve cell bodies with DBH-LI alone were generally larger (median diameter 30 m) than those with both DBH-LI and NPY-LI (median diameter 20 m). Some cell bodies showing DBH-LI alone were surrounded by boutons with NPY-LI but not DBH-LI. Axons that displayed simultaneously both substance P-LI (SP-LI) and calcitonin gene-related peptide-LI (CGRP-LI) also formed a plexus around all arteries studied, being particularly dense around the mesenteric and pulmonary arteries. These axons are most likely sensory since SP-LI was reduced by capsaicin treatment, and nerve cell bodies with both SP-LI and CGRP-LI were found in dorsal root ganglia and the vagal ganglion. A dense plexus of axons showing somatostatin-LI was located around the pulmonary artery and its main intrapulmonary branches. A few nerves with vasoactive intestinal polypeptide-LI were found around the dorsal aorta and pulmonary artery. No perivascular nerves with enkephalin-LI were observed. Reversed-phase, high-pressure liquid chromatography of acid extracts of the large arteries showed that the major peaks of NPY-LI and SP-LI coeluted with porcine NPY (1–36) and synthetic SP (1–11), respectively. Thus, the location and structure of these peptides in perivascular nerves has been highly conserved during vertebrate evolution.