neuropeptide-y and Coronary-Disease

The need for addressing posttraumatic stress disorder (PTSD) among combat veterans returning from Afghanistan and Iraq is a growing public health concern. Current PTSD management addresses psychiatric parameters of this condition. However, PTSD is not simply a psychiatric disorder. Traumatic stress increases the risk for inflammation-related somatic diseases and early mortality. The metabolic syndrome reflects the increased health risk associated with combat stress and PTSD. Obesity, dyslipidemia, hypertension, diabetes mellitus, and cardiovascular disease are prevalent among PTSD patients. However, there has been little appreciation for the need to address these somatic PTSD comorbidities. Medical professionals treating this vulnerable population should screen patients for cardiometabolic risk factors and avail themselves of existing preventive diet, exercise, and pharmacologic modalities that will reduce such risk factors and improve overall long-term health outcomes and quality of life. There is the promise that cardiometabolic preventive therapy complementing psychiatric intervention may, in turn, help improve the posttraumatic stress system dysregulation and favorably impact psychiatric and neurologic function. © 2013 S. Karger AG, Basel.

Topics: Arousal; Autonomic Nervous System Diseases; Blood Coagulation Disorders; Coronary Disease; Diabetes Complications; Dyslipidemias; Endoplasmic Reticulum Stress; Health Status; Humans; Inflammation; Insulin Resistance; Mental Healing; Mental Health; Metabolic Syndrome; Mortality, Premature; Neuropeptide Y; Neurosecretory Systems; Neurotransmitter Agents; Obesity; Risk Factors; Sleep Wake Disorders; Stress Disorders, Post-Traumatic; Suicide; Weight Gain

Topics: Animals; Coronary Disease; Humans; Myocardial Contraction; Neuropeptide Y; Stimulation, Chemical; Vasoconstrictor Agents

To investigate the effect of Shenmai injection (SMI) on neuroendocrine function in the patients with heart failure (HF).. Sixty patients with HF were randomly divided into the treated group administered with SMI combined with western medicine, and the control group administered with western medicine alone. The change of cardiac function was observed, and plasma neuropeptide Y (NPY), endothelin (ET) and atrial natriuretic polypeptide (ANP) were determined by immunoradiometric assay.. The total effective rate and markedly effective rate were higher in the treated group than that of the control group, the level of NPY, ET and ANP of both groups were higher than healthy subjects. The plasma NPY, ET and ANP of both groups were significantly reduced after treatment, the effect of treated group was better than that of control group.. SMI could improve the HF patient's cardiac function, reduce the level of plasma NPY, ET and ANP, their neuroendocrine activity was affected at the same time.

Topics: Aged; Atrial Natriuretic Factor; Coronary Disease; Drugs, Chinese Herbal; Endothelins; Female; Heart Failure; Humans; Infusions, Intravenous; Male; Middle Aged; Neuropeptide Y

Neuropeptide Y is a potent vasoconstrictor thought to enhance the development of atherosclerosis. The leucine 7 to proline 7 (Leu7Pro) polymorphism, located in the signal peptide part of the human preproneuropeptide Y, has been associated with serum lipid levels, intima-media thickness of the common carotid arteries, and diabetic retinopathy in type 2 diabetic patients. Therefore, we investigated the impact of the Leu7Pro polymorphism on diabetic nephropathy, cardiovascular risk factors, and cardiovascular disease in type 1 diabetic patients.. A total of 996 patients from the Finnish Diabetic Nephropathy study were studied in a case-control, cross-sectional study. The carrier frequency of the Pro7 substitution was 13% in the entire study population.. The Pro7 substitution was more common in patients with proteinuria than in those with a normal albumin excretion rate (16 vs. 11%, P < 0.05). Patients with the Pro7 allele had worse glycemic control (HbA(1c) 8.8 vs. 8.5%, P < 0.005), more coronary heart disease (CHD) (14 vs. 8%, P < 0.05), and higher serum triglycerides (1.65 vs. 1.35 mmol/l, P < 0.005) than patients with the wild-type genotype. There were no differences in the plasma neuropeptide Y levels between the patients with Pro7 compared with those with the wild-type genotype. The Leu7Pro polymorphism was independently associated with HbA(1c) (P < 0.001), proteinuria (P < 0.01), and CHD (P < 0.01) in multiple regression analyses.. We conclude that the Leu7Pro polymorphism may contribute to the genetic susceptibility to diabetic nephropathy and CHD in type 1 diabetic patients, possibly by influencing glycemic control and triglycerides.

Topics: Adult; Amino Acid Substitution; Blood Glucose; Body Mass Index; Cholesterol; Coronary Disease; Diabetes Mellitus, Type 1; Female; Genotype; Glycated Hemoglobin; Humans; Leucine; Male; Mutation, Missense; Neuropeptide Y; Proline; Protein Precursors; Proteinuria; Risk Factors; Triglycerides

Neuropeptide Y (NPY) is a molecule that may have both vasoconstrictive and vasodilatory actions. A common polymorphism in the human NPY gene that results in the Leucine7 to Proline7 substitution (Leu7Pro) in the signal peptide part of the NPY was recently identified. This substitution has been associated with elevated serum cholesterol levels and with slightly accelerated progression rate of carotid intima-media thickness, thus suggesting increased risk of atherosclerosis in carriers of Pro7 substitution. Recent data also indicate that subjects with Pro7 substitution may have increased endothelial release of NPY. This study was undertaken to elucidate the effects of Leu7Pro polymorphism on arterial endothelial function. We measured flow-mediated endothelial-dependent dilatation (FMD) of the brachial artery in two separate populations: in 152 middle-aged men and in 95 prepubertal children. In both study populations, subjects with Pro7 substitution had 48-52% higher FMD compared with subjects having the wildtype (Leu7/Leu7) signal peptide sequence. We conclude that Pro7 substitution in signal peptide of the NPY is associated with enhanced endothelial-dependent vasodilation. Prospective studies are needed to determine whether Pro7 substitution is associated with increased or decreased risk of cardiovascular morbidity and mortality.

Topics: Adult; Age Factors; Aged; Analysis of Variance; Blood Pressure Determination; Brachial Artery; Child; Coronary Disease; Endothelium, Vascular; Female; Genetic Predisposition to Disease; Humans; Hypercholesterolemia; Leucine; Male; Middle Aged; Neuropeptide Y; Polymorphism, Genetic; Probability; Proline; Prospective Studies; Protein Sorting Signals; Reference Values; Risk Factors; Sampling Studies; Statistics, Nonparametric; Vasodilation

Leucine 7 (Leu7) to proline 7 (Pro7) substitution in the neuropeptide Y (NPY) gene has been associated with higher serum total and low-density lipoprotein (LDL) cholesterol levels, particularly in obese subjects. We investigated the frequency of the Pro7 allele and the association of the polymorphism with serum lipid levels in patients with coronary heart disease (CHD). A total of 414 CHD patients (mean age 61 years, range 33-74) participated in the cross-sectional EUROASPIRE study. Of the subjects 39% used lipid-lowering drugs. The frequency of the Pro7 allele in CHD patients (0.082) did not differ from that in control subjects (0.071). The mean (+/-SD) serum total cholesterol concentration was higher in women with the Pro7 allele (7.57 +/- 0.57 mmol/L, n = 8) than in women with the Leu7Leu genotype (6.69 +/- 1.01 mmol/L, n = 69, P = 0.019), when subjects using lipid-lowering medication were excluded. In contrast, serum total cholesterol concentration did not significantly differ between the genotypes in men. The Leu7Pro polymorphism was not associated with serum LDL, high-density lipoprotein (HDL) cholesterol, and triglyceride concentrations. In conclusion, the Pro7 allele in the NPY gene was associated with higher serum total cholesterol concentration only in women with CHD who did not use lipid-lowering drugs.

Topics: Aged; Amino Acid Substitution; Blood Pressure; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Coronary Disease; Female; Genotype; Humans; Leucine; Lipids; Male; Middle Aged; Neuropeptide Y; Polymorphism, Genetic; Proline; Protein Precursors; Triglycerides

Neurohormones may influence vascular tone both during and after exercise. Neuropeptide Y (NPY), which is costored and released with norepinephrine (NE) during sympathetic activity, is a potent vasoconstrictor with a relatively long half-life. We therefore examined its possible association with the ischemic response to exercise in patients with coronary artery disease.. Twenty-nine male patients with effort-induced angina pectoris underwent a symptom-limited exercise test. In addition to conventional ST-segment analysis, we examined ischemia on the basis of heart rate (HR)-adjusted ST-segment changes through calculation of the ST/HR slope during the final 4 minutes of exercise and of the ST/HR recovery loop after exercise. Blood samples were taken before, during, and after exercise for an analysis of several neurohormones. Mean ST-segment depression was -223+/-20.2 microV (P:<0.0001) just before the termination of exercise, followed by a gradual normalization, but it remained significant after 10 minutes (-49+/-8.9 microV, P:<0.0001). At the end of exercise, the ST/HR slope, which reflects myocardial ischemia, was -6.0+/-0.77 microV/HR. In most patients, ST-segment levels at a given HR were lower during recovery than during exercise, here referred to as ST "deficit." Exercise increased the plasma levels of NPY, NE, epinephrine, and N-terminal proatrial natriuretic peptide, but big endothelin remained unchanged. Although NE and epinephrine peaked at maximal exercise, the highest levels of NPY and N-terminal proatrial natriuretic peptide were observed 4 minutes after exercise. The maximal increase in the NPY correlated significantly with ST-segment depression at 3 minutes after exercise (r=-0.61, P:= 0.0005), the ST deficit at the corresponding time point (r=-0.66, P:= 0.0001), and the duration of ST-segment depression after exercise (r= 0.42, P:=0.02). In contrast, no such correlations were found for NE.. The present study has for the first time demonstrated a correlation between plasma NPY levels and the degree and duration of ST-segment depression after exercise in patients with coronary artery disease, which suggests that NPY may contribute to myocardial ischemia in these patients.

Topics: Analysis of Variance; Angina Pectoris; Atrial Natriuretic Factor; Coronary Disease; Electrocardiography; Endothelin-1; Endothelins; Epinephrine; Exercise Test; Heart Rate; Humans; Male; Middle Aged; Neuropeptide Y; Norepinephrine; Protein Precursors; Time Factors

An attempt to determine the consequences of prolonged ischemia on simultaneous regional changes in norepinephrine (NE) and neuropeptide Y (NPY) interstitial myocardial concentrations in a pig model in vivo was made. The aim of the authors was to investigate further the mechanism of the major NE release previously observed in perfused hearts preserved using a Langendorff technique. Regional myocardial ischemia was induced by ligation of the left anterior descending coronary artery (LAD) in ten anesthetized pigs. NE and NPY release was studied using interstitial microdialysis, a technique initially used to monitor neurotransmitter kinetics in brain dialysate samples. Four dialysis probes were implanted into the left ventricular wall of the beating heart. Two were implanted into the ischemic region (LAD) (for NE and NPY determinations, respectively) and the remaining two into the non-ischemic left circumflex coronary artery region (LCX). Dialysate NE and NPY concentrations, as indices of interstitial myocardial NE and NPY concentrations, were measured by HPLC and RLA, respectively. A slight but significant increase in NPY levels was observed in both territories (LAD: from 190 +/- 27 to 349 +/- 62 pmol/l, LCX: 146 +/- 30 to 257 +/- 52 pmol/l) suggesting moderate stimulation of cardiac sympathetic nerve activity following LAD occlusion. On the contrary, a marked but progressive increase in NE release was observed in the ischemic region (from 8.8 +/- 1.0 to 251.4 +/- 44.8 nmol/l), when NE levels in the non-ischemic region remained stable (from 10.3 +/- 2.1 to 11.0 +/- 1.9 nmol/l). These results demonstrate the utility of regional in-vivo myocardial NE and NPY monitoring using microdialysis. The strong and sustained NE accumulation occurring in the ischemic region is consistent with the hypothesis of a local non-exocytotic metabolic NE release in case of prolonged myocardial ischemia, when exocytotic release remain only minimal as attested by the slight increase in NPY observed.

Topics: Animals; Coronary Circulation; Coronary Disease; Hemodynamics; Myocardial Ischemia; Myocardium; Neuropeptide Y; Norepinephrine; Swine; Time Factors

In the present study, the cardiac outflow of endothelin, noradrenaline and neuropeptide Y was investigated in 13 patients undergoing first time coronary angioplasty (PTCA) due to stenosis of the left anterior descending coronary artery. During PTCA there was an increase in the coronary sinus levels of endothelin but no detectable changes in neuropeptide Y or noradrenaline concentrations. It is therefore concluded that endothelial damage rather than myocardial ischaemia is the cause of endothelin release during PTCA.

Topics: Angioplasty, Balloon, Coronary; Chromatography, High Pressure Liquid; Coronary Disease; Endothelins; Endothelium, Vascular; Humans; Myocardial Ischemia; Myocardium; Neuropeptide Y; Norepinephrine; Radioimmunoassay

1. The effects of calcitonin gene-related peptide (CGRP) and neuropeptide Y (NPY) were examined on sheep circumflex (2-2.5 mm o.d.) coronary artery rings, with and without endothelium, under oxygenated, hypoxic and simulated ischaemic conditions. The interaction between the vasoconstrictor effects of NPY and the thromboxane mimetic, U46619, was also studied. 2. Ischaemia was simulated by modification of the composition of the physiological salt solution by increasing potassium and H+, including lactate and reducing glucose and PO2. 3. Hypoxia alone and simulated ischaemia increased the maximum vasodilatation produced by CGRP. CGRP (30 nM) abolished and markedly reduced the contraction that was induced by hypoxia and simulated ischaemia respectively. 4. Hypoxia increased and simulated ischaemia reduced the contractile response to NPY in endothelium intact rings. When the endothelium was removed, NPY caused a contraction under ischaemic conditions only. The hypoxic and ischaemic-induced contractions were augmented by NPY (30 nM). 5. In the rings containing endothelium, NPY enhanced the contraction caused by U46619 during hypoxia only. In endothelium-denuded preparations, NPY increased or partially restored the contraction caused by U46619. 6. These results show that the responsiveness of coronary artery rings isolated from sheep to either CGRP or NPY is modified by hypoxia or simulated myocardial ischaemia.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Animals; Calcitonin Gene-Related Peptide; Coronary Disease; Coronary Vessels; Endothelium, Vascular; Hypoxia; In Vitro Techniques; Muscle, Smooth, Vascular; Neuropeptide Y; Potassium Chloride; Prostaglandin Endoperoxides, Synthetic; Sheep

Topics: Animals; Coronary Circulation; Coronary Disease; Dogs; Indomethacin; Neuropeptide Y; Neuropeptides; Neurotensin; Phenoxybenzamine; Propranolol; Prostaglandin-Endoperoxide Synthases

(1) The possible influence of prostaglandins (PG) E1 and I2 as well as ischaemia, ouabain and bradykinin on the outflow of calcitonin gene-related peptide (CGRP)- and neuropeptide Y (NPY)-like immunoreactivity (LI) from the guinea-pig heart was studied in vitro. (2) Exposure to PGE1 (10(-5) M), but not PGI2 (10(-5) M), induced an increased outflow, suggesting release of CGRP-LI. PGE1 simultaneously increased the contractile force and heart rate while no effects were observed on perfusate volume or outflow of NPY-LI. PGI2 had no effect on contractile parameters or coronary flow. In separate experiments on capsaicin-pretreated animals, the stimulatory effects of PGE1 on heart rate and contractile force remained unchanged while no increased CGRP-LI outflow was detectable. (3) Ouabain, bradykinin and reperfusion after total stop-flow ischaemia was associated with an indomethacin-resistant increase in perfusate levels of CGRP-LI but not of NPY-LI. While ouabain markedly increased the contractile force, exposure to bradykinin or ischaemia did not induce any clear-cut changes in contractile force or heart rate. (4) Capsaicin-exposure evoked a markedly increased outflow of CGRP-LI but not of NPY-LI in combination with an increase in heart rate and a decrease in contractile force. Repeated administration of capsaicin induced tachyphylaxis. The stimulatory effects of capsaicin on CGRP-LI outflow and heart rate, but not the negative inotropic effect, did not occur in capsaicin-pretreated animals. (5) It is concluded that PGE1, but not PGI2, can activate cardiac capsaicin-sensitive fibres as revealed by increased outflow of CGRP-LI.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Alprostadil; Animals; Bradykinin; Calcitonin Gene-Related Peptide; Capsaicin; Coronary Disease; Epoprostenol; Guinea Pigs; Heart; In Vitro Techniques; Indomethacin; Myocardium; Neurons, Afferent; Neuropeptide Y; Ouabain; Prostaglandins; Sympathetic Nervous System

Neuropeptide-Y (NPY), a brain peptide, is located in the walls of human coronary arteries. This study assessed the effects of NPY on the coronary circulation in 40 chloralose-anesthetized, open-chest dogs. Intracoronary NPY (42 nmol over 5.2 min) caused a 39% reduction in coronary blood flow without changing heart rate or aortic pressure. To determine whether this vasoconstriction could produce ischemia, intramyocardial pH was measured in seven dogs (group I) and decreased from 7.45 +/- 0.06 to 7.37 +/- 0.06 pH units after NPY in the subendocardium (P less than 0.0002), and from 7.45 +/- 0.06 to 7.40 +/- 0.05 pH units (P less than 0.04) in the subepicardium of the infused zone. Left ventricular ejection fraction (LVEF), measured by radionuclide angiography, decreased from 0.52 +/- 0.08 to 0.42 +/- 0.12 U (n = 5, P less than 0.01) during NPY. NPY-induced vasoconstriction was also associated with ST-T wave changes on the electrocardiogram (ECG) in eight of nine other animals (group V). In another group of six dogs (group IV), the change in small vessel resistance accounted for 94% of the increase in total resistance, so that the primary vasoconstrictor effect of NPY was exerted on small coronary arteries. Thus, NPY, a peptide found in human coronary arteries, caused constriction of primarily small coronary arteries that was severe enough to produce myocardial ischemia as determined by ECG ST-T wave changes, and decreases in intramyocardial pH and LVEF in dogs.

Topics: Animals; Coronary Circulation; Coronary Disease; Coronary Vessels; Dogs; Heart Rate; Humans; Hydrogen-Ion Concentration; Injections, Intra-Arterial; Neuropeptide Y; Stroke Volume; Vascular Resistance; Vasoconstrictor Agents

1. In order to examine the concentration of neuropeptide Y-like immunoreactivity (NPY-LI) and atrial natriuretic peptide (ANP) in the circulation in man, blood was sampled from the iliac vein, the inferior vena cava, the superior vena cava, the pulmonary artery and the femoral artery in 13 patients undergoing cardiac catheterization. 2. Plasma NPY-LI levels were similar at all points sampled and no arteriovenous differences were found. Plasma ANP concentration in the pulmonary artery was greater than in peripheral venous blood but there was a strong correlation between the two. 3. The concentration of NPY-LI and ANP in peripheral venous blood reflects central venous and arterial concentrations.

Topics: Adult; Aged; Atrial Natriuretic Factor; Cardiac Catheterization; Coronary Disease; Female; Femoral Artery; Femoral Vein; Humans; Male; Middle Aged; Neuropeptide Y; Pulmonary Artery; Venae Cavae