neuropeptide-y and Hypertrophy--Left-Ventricular

I review recent knowledge on the interference of neuropeptide Y with energy balance and cardiovascular and renal disease and on the central regulation of bone mass.. Although neuropeptide Y is mainly seen as a vasoconstrictor, rats overexpressing the neuropeptide Y gene show reduced blood pressure and longer life span in comparison with control rats. Due to its strong mitogenic effects on vascular smooth muscle cells, neuropeptide Y induces occlusive lesions in a rat model of atherosclerosis induced by balloon angioplasty. The involvement of neuropeptide Y in experimental atherosclerosis is complex and may include also favourable, compensatory, mechanisms because, at physiological concentrations, it also activates a potent neoangiogenic response to ischemia. Subjects with a common genotype in the neuropeptide Y gene, which underlies increased intracellular neuropeptide Y storage, display slightly raised blood pressure, high serum cholesterol and increased carotid intima media thickness. In patients with end-stage renal disease high neuropeptide Y in plasma has been associated consistently with concentric left-ventricular hypertrophy and cardiovascular mortality. Finally, recent studies have shown that neuropeptide Y constitutes an important central regulator of bone mass and that it may be involved in inflammation and immune regulation.. Evidence has accrued in experimental animals that altered neuropeptide Y is involved in obesity and the attendant metabolic complications. Recent data also suggest that this peptide may play a role in atherosclerosis and related cardiovascular complications.

Topics: Animals; Body Weight; Bone and Bones; Cardiovascular Diseases; Energy Metabolism; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Neuropeptide Y; Rats

Topics: Angiotensin II; Animals; Arginine Vasopressin; Atrial Natriuretic Factor; Blood Pressure; Bradykinin; Humans; Hypertrophy, Left Ventricular; Neuropeptide Y; Peptides; Renin-Angiotensin System

The aim or the study was to assess plasma neuropeptide Y immunoreactivity concentration (NPY-ir) during dynamic exercise in pts with different stages of essential hypertension (ESH). We studied 25 males aged 29.4 +/- 6.3 yrs with established ESH (ESH) and 12 healthy males aged 27.3 +/- 5.1 yrs (C). Plasma concentrations of NPY-ir, NA, A, BP were measured before treadmill test, in the last minute of two six-min. work loads corresponding to 60% and 80% of maximal individual load and 30 min. after cessation of exercise. Plasma NPY-ir was evaluated with RIA, NA and A with REA. Gradual exercise resulted in an increase of NPY-ir in ESH (from 14.4 +/- 5.8 to 18.1 +/- 6.4 and 20.7 +/- 8.1 fmol/ml p = 0.036, p = 0.02) and in C (from 11.7 +/- 4.6 to 13.4 +/- 5.0 and 15.2 +/- 5.9 fmol/ml, p < 0.01). Likewise plasma NA and A increased in both groups. Plasma NPY-ir during exercise was significantly higher in ESH than in C (p = 0.041 and p = 0.047) while no such differences were observed in plasma NA and A. According to the left ventricle mass index (LVMI) ESH was divided into two subgroups: with left ventricular hypertrophy (LVH+) n = 10, LVMI = 159.7 +/- 7.7 g/m2 and without the hypertrophy (LVH-) n = 15 LVMI = 112.3 +/- 19.2g/m2. LVH- presented significant increase in plasma NPY-ir during exercise (from 14.7 +/- 5.7 to 18.2 +/- 6.5, 22.8 +/- 8.3 fmol/ml p < 0.01), while no changes in LVH+ were observed (from 14.1 +/- 5.8 to 17.8 +/- 6.0 and 17.8 +/- 6.7 fmol/ml, ns). LVH+ were older than LVH- (33.4 +/- 7.1 yrs vs 26.7 +/- 4.2 p = 0.04), but no correlation between age and plasma NPY-ir was noticed. No differences in plasma NA and A were present between these subgroups.. Patients at different stages of essential hypertension display various patterns of sympatho-adrenal activation during dynamic exercise.

Topics: Adult; Blood Pressure; Epinephrine; Exercise; Exercise Test; Heart Rate; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Neuropeptide Y; Norepinephrine; Prohibitins

Cyclic guanosine monophosphate-protein kinase G-phosphodiesterase 5 signaling may be disturbed in heart failure (HF) with preserved ejection fraction, contributing to cardiac remodeling and dysfunction. The purpose of this study was to manipulate cyclic guanosine monophosphate signaling using the dipeptidyl-peptidase 4 inhibitor saxagliptin and phosphodiesterase 5 inhibitor tadalafil. We hypothesized that preservation of cyclic guanosine monophosphate cGMP signaling would attenuate pathological cardiac remodeling and improve left ventricular (LV) function.. We assessed LV hypertrophy and function at the organ and cellular level in aortic-banded pigs. Concentric hypertrophy was equal in all groups, but LV collagen deposition was increased in only HF animals. Prevention of fibrotic remodeling by saxagliptin and tadalafil was correlated with neuropeptide Y plasma levels. Saxagliptin better preserved integrated LV systolic and diastolic function by maintaining normal LV chamber volumes and contractility (end-systolic pressure-volume relationship, preload recruitable SW) while preventing changes to early/late diastolic longitudinal strain rate. Function was similar to the HF group in tadalafil-treated animals including increased LV contractility, reduced chamber volume, and decreased longitudinal, circumferential, and radial mechanics. Saxagliptin and tadalafil prevented a negative cardiomyocyte shortening-frequency relationship observed in HF animals. Saxagliptin increased phosphodiesterase 5 activity while tadalafil increased cyclic guanosine monophosphate levels; however, neither drug increased downstream PKG activity. Early mitochondrial dysfunction, evident as decreased calcium-retention capacity and Complex II-dependent respiratory control, was present in both HF and tadalafil-treated animals.. Both saxagliptin and tadalafil prevented increased LV collagen deposition in a manner related to the attenuation of increased plasma neuropeptide Y levels. Saxagliptin appears superior for treating heart failure with preserved ejection fraction, considering its comprehensive effects on integrated LV systolic and diastolic function.

Topics: Adamantane; Animals; Atrial Natriuretic Factor; Cyclic GMP; Dipeptides; Dipeptidyl-Peptidase IV Inhibitors; Disease Models, Animal; Echocardiography; Hypertrophy, Left Ventricular; Male; Natriuretic Peptide, Brain; Neuropeptide Y; Phosphodiesterase 5 Inhibitors; Signal Transduction; Swine; Swine, Miniature; Tadalafil; Ventricular Function, Left

Metabolism remodeling has been recognized as an early event following cardiac pressure overload. However, its temporal association with ventricular hypertrophy has not been confirmed. Moreover, whether trimetazidine could favorably affect this process also needs to be determined. The aim of the study was to explore the temporal changes of myocardial metabolism remodeling following pressure-overload induced ventricular hypertrophy and the potential favorable effect of trimetazidine on myocardial metabolism remodeling.. A rat model of abdominal aortic constriction (AAC)-induced cardiac pressure overload was induced. These rats were grouped as the AAC (no treatment) or TMZ group according to whether oral trimetazidine (TMZ, 40 mg/kg/d, for 5 days) was administered. Changes in cardiac structures were sequentially evaluated via echocardiography. The myocardial ADP/ATP ratio was determined to reflect the metabolic status, and changes in serum neuropeptide Y systems were evaluated.. Myocardial metabolic disorder was acutely induced as evidenced by an increased ADP/ATP ratio within 7 days of AAC before the morphological changes in the myocardium, accompanied by up-regulation of serum oxidative stress markers and expression of fetal genes related to hypertrophy. Moreover, the serum NPY and myocardial NPY-1R, 2R, and 5R levels were increased within the acute phase of AAC-induced cardiac pressure overload. Pretreatment with TMZ could partly attenuate myocardial energy metabolic homeostasis, decrease serum levels of oxidative stress markers, attenuate the induction of hypertrophy-related myocardial fetal genes, inhibit the up-regulation of serum NPY levels, and further increase the myocardial expression of NPY receptors.. Cardiac metabolic remodeling is an early change in the myocardium before the presence of typical morphological ventricular remodeling following cardiac pressure overload, and pretreatment with TMZ may at least partly reverse the acute metabolic disturbance, perhaps via regulation of the NPY system.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Animals; Aorta, Abdominal; Arterial Pressure; Cardiovascular Agents; Constriction; Disease Models, Animal; Energy Metabolism; Gene Expression Regulation; Hypertrophy, Left Ventricular; Male; Myocardium; Neuropeptide Y; Oxidative Stress; Rats, Wistar; Receptors, G-Protein-Coupled; Receptors, Neuropeptide; Receptors, Neuropeptide Y; Signal Transduction; Trimetazidine; Ventricular Function, Left; Ventricular Remodeling

Neuropeptide Y (NPY) is a sympathetic neurotransmitter that acts on multiple receptors involved in cardiovascular remodelling and angiogenesis. Plasma levels of NPY are increased in patients with end-stage renal disease (ESRD) and are independently related to left ventricular hypertrophy (LVH) and incident cardiovascular events in these patients.. To investigate the relationship between NPY receptor Y2 gene polymorphism and left ventricular mass index (LVMI) as well as the interaction between this polymorphism and plasma NPY in determining LVH in 189 ESRD patients.. LVMI was significantly higher (+12%, P = 0.03) in patients carrying the C allele than in those without C allele and was linearly associated with plasma NPY (P = 0.01). Interaction analysis showed a significant NPY-LVMI relationship in patients with the C allele, both at univariate (r = 0.27, P = 0.001) and multivariate (r = 0.21, P = 0.01) analyses, whereas no such relationship existed in patients without this allele. In fully adjusted analyses, a 10 pmol/l increase in plasma NPY entailed a 4.9 g/m increase in LVMI in patients with C allele, whereas the same change in NPY levels did not modify the NPY-LVMI link in patients without such allele (P = 0.009).. NPY receptor Y2 polymorphism is independently associated with LVMI and interacts with plasma levels of NPY in explaining the variability of LVH in ESRD. These results offer a genetic basis to the hypothesis that NPY is causally implicated in the pathogenetic pathway leading to LVH in ESRD patients.

Topics: Comorbidity; Female; Genetic Predisposition to Disease; Humans; Hypertrophy, Left Ventricular; Italy; Kidney Failure, Chronic; Logistic Models; Male; Middle Aged; Neuropeptide Y; Polymorphism, Single Nucleotide; Receptors, Neuropeptide Y; Renal Dialysis

The secretory prohormone chromogranin A (CHGA) is overexpressed in essential hypertension, a complex trait with genetic predisposition, while its catecholamine release-inhibitory fragment catestatin is diminished, and low catestatin predicts augmented adrenergic pressor responses. These findings from studies on humans suggest a mechanism whereby diminished catestatin might increase the risk for hypertension. We generated Chga and humanized mice through transgenic insertion of a human CHGA haplotype in order to probe CHGA and catestatin in vivo. Chga mice displayed extreme phenotypic changes, including: (a) decreased chromaffin granule size and number; (b) elevated BP; (c) loss of diurnal BP variation; (d) increased left ventricular mass and cavity dimensions; (e) decreased adrenal catecholamine, neuropeptide Y (Npy), and ATP contents; (f) increased catecholamine/ATP ratio in the chromaffin granule; and (g) increased plasma catecholamine and Npy levels. Rescue of elevated BP to normalcy was achieved by either exogenous catestatin replacement or humanization of Chga mice. Loss of the physiological "brake" catestatin in Chga mice coupled with dysregulation of transmitter storage and release may act in concert to alter autonomic control of the circulation in vivo, eventuating in hypertension.

Topics: Animals; Blood Pressure; Chromaffin Granules; Chromogranin A; Chromogranins; Circadian Rhythm; Corticosterone; Epinephrine; Gene Targeting; Humans; Hypertension; Hypertrophy, Left Ventricular; Mice; Mice, Knockout; Mice, Transgenic; Microscopy, Electron; Neuropeptide Y; Norepinephrine; Renin

Left ventricular hypertrophy (LVH) in patients with arterial hypertension is closely related to the levels of blood pressure (BP), catecholamines, angiotensin II and other mitogenic peptides. Pheochromocytoma (pheo) is a type of hypertension caused by excessive production of catecholamines. The aim of this study was to determinate if left ventricular hypertrophy in patients with pheochromocytoma is related to catecholamines and neuropeptide Y (NPY).. 29 patients with pheochromocytoma (22 F, age 40 +/- 13 years), plasma concentration of neuropeptide Y immunoreactivity, noradrenaline (NA), and adrenaline (A) were determined. Twenty-four hour urine collection for determination of noradrenaline and adrenaline were performed. Every patient had echocardiographic examination and 24 h ambulatory blood pressure monitoring.. Left ventricular hypertrophy was diagnosed in 14 patients. No differences in systolic and diastolic blood pressure in patients with and without left ventricular hypertrophy were found. Plasma noradrenaline and adrenaline levels did not differ between both groups, while plasma neuropeptide Y immunoreactivity was higher in patients with left ventricular hypertrophy than in patients without left ventricular hypertrophy (18.46 +/- 13.26 vs. 9.3 +/- 5.9 fmol/ml (p = 0.02)). Left ventricular mass index (LVMI) correlated with plasma neuropeptide Y-immunoreactivity (r = 0.42 p = 0.023), however, no relationship between left ventricular mass index and plasma or urine noradrenaline and adrenaline levels were found.. Our results indicate that mitogenic effect of neuropeptide Y may play a role in pathogenesis of left ventricular hypertrophy in patients with pheochromocytoma.

Topics: Adrenal Gland Neoplasms; Adult; Blood Pressure; Catecholamines; Electrocardiography; Epinephrine; Female; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Neuropeptide Y; Norepinephrine; Pheochromocytoma

To investigate the relations between left ventricular hypertrophy and systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), neuropeptide Y (NPY) during cardiac hypertrophy and regression.. Blood pressure and heart rate were recorded with polygraph channel biologic message system. NPY in plasma and myocardium were measured with Radioimmunoassay. Correlation coefficient were calculated with SPSS software.. There were positive correlations between SBP, DBP, MAP, NPY in the cardiac tissue and cardiac coefficient (LVW/BW). There was no correlations between cardiac coefficient and heart rate (HR), NPY in plasma.. Hypertension is one of cardiac hypertrophy factors, SBP correlate better with LVW/ BW than DBP. SBP, DBP, MAP, NPY in cardiac tissue has correlative tendency with LVW/BW.

Topics: Animals; Blood Pressure; Heart Rate; Hypertension; Hypertrophy, Left Ventricular; Male; Neuropeptide Y; Rats; Rats, Wistar

Neuropeptide Y (NPY) is released during sympathetic stimulation and mediates the central effects of the adipostatic hormone leptin. The plasma concentration of NPY and leptin is increased in patients with end stage renal disease (ESRD), but it is unknown whether these substances are related to biochemical markers of sympathetic activity and to alterations in left ventricular (LV) mass and function in these patients.. We investigated the relationship between NPY, norepinephrine (NE), leptin and echocardiographic measurements in a cross-sectional study in 198 patients with ESRD.. NPY was directly related to plasma NE and heart rate but it was largely independent of arterial pressure and of retention of metabolic waste products. NPY was significantly higher in patients with LV hypertrophy and in those with LV systolic dysfunction than in those without these alterations. Of note, NPY emerged as an independent correlate of LV mass index and of LV ejection fraction (LVEF) (both P

Topics: Adult; Aged; Biomarkers; Cohort Studies; Cross-Sectional Studies; Echocardiography; Female; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Myocardium; Neuropeptide Y; Norepinephrine; Risk Factors; Ventricular Dysfunction, Left

The present study was performed to measure concentrations of plasma noradrenaline and neuropeptide-Y-like immunoreactivity in relation to cardiac function in patients with systemic sclerosis (SSc).. Plasma noradrenaline was measured by high performance liquid chromatography and neuropeptide-Y by radioimmunoassay in 30 consecutive patients with SSc and 48 sex and age matched controls. Left ventricular (LV) function was evaluated by Echocardiography.. There were no significant differences between patients and controls in either plasma noradrenaline or plasma neuropeptide-Y. LV dysfunction and hypertrophy were common among patients. Plasma Neuropeptide-Y was related only to systolic function, while noradrenaline was related to both systolic and diastolic function as well as to LV hypertrophy.. Patients with SSc develop different forms of myocardial dysfunction without activation of the sympathetic nervous system as evaluated by plasma noradrenaline and neuropeptide-Y; leaving vascular disease of the heart to be a main candidate.

Topics: Adult; Aged; Biomarkers; Chromatography, High Pressure Liquid; Echocardiography; Electrocardiography; Female; Heart; Hemodynamics; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Neuropeptide Y; Norepinephrine; Radioimmunoassay; Reference Values; Scleroderma, Systemic; Ventricular Function, Left

Adrenergic markers and neuropeptide Y (NPY) were examined in Dahl NaCl-sensitive and -resistant outbred male rats, fed either 0.35% or 8% NaCl diets for 8 weeks. The high salt diet caused left ventricular hypertrophy in sensitive rats but not in the resistant strain. Norepinephrine stores were not affected by high salt intake, but tyrosine hydroxylase, and dopamine beta-hydroxylase were elevated in the salt-induced hypertrophied left ventricle in conjunction with increased levels of nerve growth factor and p75 neurotrophin receptor. In contrast, high salt intake reduced ventricular neuropeptide Y in both Dahl salt-resistant and -sensitive rats.

Topics: Adrenergic Agents; Animals; Hypertrophy, Left Ventricular; Male; Myocardium; Nerve Growth Factors; Neuropeptide Y; Norepinephrine; Rats; Rats, Inbred Dahl; Sodium Chloride, Dietary; Sympathetic Nervous System

The aims of the study were to determine the effect of chronic pressure overload of the left ventricle on the density and distribution of neuropeptide-Y-like immunoreactive (NPY-LI) nerve fibres in heart and to compare any changes to those observed in adrenergic nerve fibres, identified by dopamine beta-hydroxylase immunoreactivity.. Pressure overload was produced in female adult guinea pigs by constriction of the abdominal aorta, using a modified Weck haemoclip. The same operation was performed on a separate group of animals except that no clip was placed around the aorta. Five weeks after surgery, animals were anaesthetised, and the hearts were fixed by perfusion for immunohistochemistry. Cryostat sections were stained, using an indirect peroxidase/antiperoxidase method, for NPY or dopamine beta-hydroxylase.. Aortic stenosis caused a 45% increase in left ventricular weight and a 58% increase in left atrial weight at 5 weeks postsurgery. Pulmonary oedema, a sign of cardiac failure, was evident in most of the animals with aortic stenosis. Immunohistochemical studies showed that in atria and right ventricles from animals with abdominal aortic stenosis the distribution and density of NPY-LI nerve fibres were similar to those in the sham operated guinea pigs. However, the left ventricles obtained from the animals with aortic stenosis were nearly devoid of NPY-LI nerve fibres. The density of dopamine beta-hydroxylase-LI nerve fibres was also substantially reduced in the hypertrophied left ventricles.. Aortic stenosis resulting in left ventricular hypertrophy caused a nearly complete loss of NPY-LI and dopamine beta-hydroxylase-LI nerve fibres from the left ventricle. The parallel reduction in both neuropeptide Y and dopamine beta-hydroxylase is in accordance with the association of neuropeptide Y with sympathetic (adrenergic) nerve fibres in the left ventricle and suggests that chronic left ventricular hypertrophy causes a severe degeneration of sympathetic axons supplying this chamber and/or reduces the ability of these sympathetic neurones to maintain normal levels of neurotransmitter related enzymes and neuropeptides.

Topics: Animals; Disease Models, Animal; Dopamine beta-Hydroxylase; Female; Guinea Pigs; Heart Ventricles; Hypertrophy, Left Ventricular; Immunohistochemistry; Nerve Fibers; Neuropeptide Y; Organ Size