vasoactive-intestinal-peptide and Heart-Failure

Topics: Acute Kidney Injury; Amino Acid Sequence; Animals; Asthma; Atrial Natriuretic Factor; Bronchodilator Agents; Heart Failure; Humans; Lung; Molecular Sequence Data; Neuropeptides; Peptide Fragments; Pituitary Adenylate Cyclase-Activating Polypeptide; Vasoactive Intestinal Peptide; Vasodilator Agents

Our primary objective was to compare the effects of three different doses of candoxatrilat with the effects of placebo on urinary volume in patients with moderately severe heart failure. The effects of candoxatrilat on urinary composition, neuroendocrine indexes and renal hemodynamic function were also studied.. Candoxatrilat, a neutral endopeptidase inhibitor, reduces degradation of atrial natriuretic peptide and provokes diuresis in patients with mild heart failure, but the renal effects have not been studied in patients with moderately severe heart failure in a placebo-controlled study.. In a double-blind crossover trial, the effects of intravenous boluses of saline vehicle (placebo) and 50, 100 and 200 mg of candoxatrilat were compared on separate days in 12 patients with heart failure. Urinary output and composition were measured for 8 h. Renal blood flow and glomerular filtration rate were determined by radionuclide techniques. Blood was withdrawn for the measurement of hormones before and 3 h after dosing.. All doses of candoxatrilat increased urinary volume (e.g., [mean +/- SEM] 263 +/- 53 to 490 +/- 82 ml for saline solution and the 200-mg dose, respectively, p < 0.01) and sodium content (14 +/- 4 to 37 +/- 11 mmol, p < 0.001) in the 1st 4 h after dosing. Plasma atrial natriuretic peptide increased (140 +/- 26 to 279 +/- 37 pg/ml, p < 0.01), whereas aldosterone decreased (178 +/- 41 to 125 +/- 35 pg/ml, p < 0.01), and renin activity was unchanged (10 +/- 2 to 12 +/- 3 ng/ml per h).. Candoxatrilat given acutely causes diuresis, even in patients with moderately severe heart failure.

Topics: Aged; Aldosterone; Atrial Natriuretic Factor; Cross-Over Studies; Cyclic GMP; Cyclohexanecarboxylic Acids; Diuresis; Double-Blind Method; Drug Administration Schedule; Electrolytes; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Neprilysin; Renal Circulation; Sodium; Urine; Vasoactive Intestinal Peptide

Postganglionic cardiac parasympathetic and sympathetic nerves are physically proximate in atrial cardiac tissue allowing reciprocal inhibition of neurotransmitter release, depending on demands from central cardiovascular centers or reflex pathways. Parasympathetic cardiac ganglion (CG) neurons synthesize and release the sympathetic neurotrophin nerve growth factor (NGF), which may serve to maintain these close connections. In this study we investigated whether NGF synthesis by CG neurons is altered in heart failure, and whether norepinephrine from sympathetic neurons promotes NGF synthesis. NGF and proNGF immunoreactivity in CG neurons in heart failure rats following chronic coronary artery ligation was investigated. NGF immunoreactivity was decreased significantly in heart failure rats compared to sham-operated animals, whereas proNGF expression was unchanged. Changes in neurochemistry of CG neurons included attenuated expression of the cholinergic marker vesicular acetylcholine transporter, and increased expression of the neuropeptide vasoactive intestinal polypeptide. To further investigate norepinephrine's role in promoting NGF synthesis, we cultured CG neurons treated with adrenergic receptor (AR) agonists. An 82% increase in NGF mRNA levels was detected after 1h of isoproterenol (β-AR agonist) treatment, which increased an additional 22% at 24h. Antagonist treatment blocked isoproterenol-induced increases in NGF transcripts. In contrast, the α-AR agonist phenylephrine did not alter NGF mRNA expression. These results are consistent with β-AR mediated maintenance of NGF synthesis in CG neurons. In heart failure, a decrease in NGF synthesis by CG neurons may potentially contribute to reduced connections with adjacent sympathetic nerves.

Topics: Adrenergic alpha-Agonists; Adrenergic Antagonists; Adrenergic beta-Agonists; Animals; Cells, Cultured; Heart; Heart Failure; Isoproterenol; Male; Nerve Growth Factor; Nerve Growth Factors; Neurons; Parasympathetic Nervous System; Phenylephrine; Protein Precursors; Rats; Rats, Sprague-Dawley; Receptors, Adrenergic; RNA, Messenger; Time Factors; Vasoactive Intestinal Peptide; Vesicular Acetylcholine Transport Proteins

Vasoactive Intestinal Peptide (VIP), a pulmonary vasodilator and inhibitor of vascular smooth muscle proliferation, is absent in pulmonary arteries of patients with idiopathic pulmonary arterial hypertension (PAH). We previously determined that targeted deletion of the VIP gene in mice leads to PAH with pulmonary vascular remodeling and right ventricular (RV) dilatation. Whether the left ventricle is also affected by VIP gene deletion is unknown. In the current study, we examined if VIP knockout mice (VIP(-/-)) develop both right (RV) and left ventricular (LV) cardiomyopathy, manifested by LV dilatation and systolic dysfunction, as well as overexpression of genes conducive to heart failure.. We examined VIP(-/-)and wild type (WT) mice using Magnetic Resonance Imaging (MRI) for evidence of cardiomyopathy associated with biventricular dilation and wall thickness changes. Lung tissue from VIP(-/-) and WT mice was subjected to whole-genome gene microarray analysis.. Lungs from VIP(-/-) mice showed overexpression of cardiomyopathy genes: Myh1 was upregulated 224 times over WT, and Mylpf was increased 72 fold. Tnnt3 was increased 105 times and tnnc2 181 fold. Hearts were dilated in VIP(-/-) mice, with thinning of LV wall and increase in RV and LV chamber size, though RV enlargement varied. Weights of VIP(-/-) mice were consistently lower.. Critically-important heart failure-related genes are upregulated in VIP(-/-) mice associated with the spontaneous cardiomyopathy phenotype, involving both left and right ventricles, suggesting that loss of the VIP gene orchestrates a panoply of pathogenic genes which are detrimental to both left and right cardiac homeostasis.

Topics: Animals; Cardiomyopathies; Female; Gene Deletion; Heart Failure; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Oligonucleotide Array Sequence Analysis; Phenotype; Stroke Volume; Transcriptome; Up-Regulation; Vasoactive Intestinal Peptide

Pulmonary hypertension (PH) leads to an increased right ventricular workload, cardiac failure and death. In idiopathic pulmonary arterial hypertension (PAH) the vasodilating vasoactive intestinal peptide (aviptadil) is deficient. The aim of the present study was to test the acute effects on haemodynamics and blood gases, and the safety, of a single dose of inhaled aviptadil in chronic PH. A total of 20 patients with PH (PAH in nine, PH in lung disease in eight and chronic thromboembolic PH in three) inhaled a single 100-microg dose of aviptadil during right-heart catheterisation. Haemodynamics and blood gases were measured. Aviptadil aerosol caused a small and temporary but significant selective pulmonary vasodilation, an improved stroke volume and mixed venous oxygen saturation. Overall, six patients experienced a pulmonary vascular resistance reduction of >20%. In patients with significant lung disease, aviptadil tended to improve oxygenation. The pulmonary vasodilating effect of aviptadil aerosol was modest and short-lived, did not cause any side-effects and led to a reduced workload of the right ventricle without affecting systemic blood pressure. Aviptadil inhalation tended to improve oxygenation in patients with significant lung disease. Further studies are needed to evaluate the full therapeutic potential of aviptadil aerosol, including higher doses and chronic treatment.

Topics: Adult; Aerosols; Aged; Blood Pressure; Drug Combinations; Female; Heart Failure; Heart Ventricles; Humans; Hypertension, Pulmonary; Lung Diseases; Male; Middle Aged; Oxygen; Phentolamine; Vasoactive Intestinal Peptide

Vasoactive intestinal peptide (VIP) is a powerful vasodilatory neuropeptide with positive inotropic and chronotropic properties. The aim of the study was to investigate the pathophysiological role of VIP in heart failure.. VIP was assayed in plasma within the first in-hospital day in 52 patients with heart failure due to dilated cardiomyopathy. The concentration of VIP was: (i) higher in patients than in healthy subjects; (ii) higher in elderly but not in younger patients compared with healthy controls; (iii) inversely related to NYHA class: higher in NYHA 2 than in NYHA > 2 patients and in normal subjects, in both young and elderly groups; (iv) not correlated with echocardiographic parameters and (v) not influenced by the aetiology of dilated cardiomyopathy.. The physiological properties of VIP suggest that the increased plasma concentrations in patients with heart failure contribute to restore the compromised haemodynamic balance either by improving myocardial performance or by counteracting the harmful effects related to simultaneous activation of other neuroendocrine systems, i.e. the sympathetic and renin-angiotensin systems. Decreased VIP concentrations are related to progressive worsening of heart failure. The higher VIP concentrations in elderly patients compared with healthy controls suggest that the capacity to increase VIP production is preserved in older people.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Biomarkers; Cardiomyopathy, Dilated; Case-Control Studies; Female; Heart Failure; Humans; Male; Middle Aged; Regression Analysis; Vasoactive Intestinal Peptide

The aim of our study was to investigate the pathophysiological role of the vasoactive intestinal peptide (VIP), a vasodilating neuropeptide with positive inotropic and chronotropic properties, in heart failure.. The study was carried out in 35 patients with heart failure due to dilated cardiomyopathy, who underwent a peripheral venous blood sample for radioimmunoassay of VIP within the first in-hospital day.. The plasma concentration of VIP: 1) is not higher than normal in the whole group of patients with heart failure; 2) is higher in younger than in elderly healthy subjects but does not significantly change in relation to age in heart disease patients; 3) is higher in elderly (> 60 years) but not in younger (< 60 years) patients compared to healthy subjects of the same age; 4) is higher in NYHA functional class 2 than in NYHA functional class > 2 groups and in normal subjects; 5) is not correlated with echocardiographic parameters; 6) does not significantly change with respect to the etiology of dilated cardiomyopathy.. The plasma concentration of VIP in heart failure is conditioned by some epidemiological and clinical variables. Unlike the healthy group, differences are not detectable with respect to the age of patients; thus, in elderly heart disease subjects the neuropeptide productive potentiality is preserved. Taking into account the physiological properties of VIP, its plasma increase in the initial phase of heart failure can be reasonably regarded as a further mechanism to restore the compromised hemodynamic balance. Its decrease, related to worse clinical conditions, could be due to a progressive depletion from the pre-synaptic nerve endings and to a deficiency in the neurogenic productive capacity of the molecule.

Topics: Adult; Aged; Aged, 80 and over; Aging; Female; Heart Failure; Humans; Male; Middle Aged; Radioimmunoassay; Reference Values; Vasoactive Intestinal Peptide; Veins

Previous studies have established short-term variability in the circulating plasma levels of cardiac peptides such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). Our aim was to investigate whether such variable patterns could be observed in other vasoactive peptides.. We measured the immunoreactivity of vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), endothelin-1 (ET-1) and calcitonin gene-related peptide (CGRP) in peripheral venous plasma collected at 2-min intervals over a 20-min period from patients with chronic cardiac failure (CCF) and from control subjects. In a second study, blood samples were obtained at 2-min intervals from the pulmonary artery, femoral artery and antecubital vein from patients with normal cardiac function while right atrial pressure and heart rate were constant.. Peripheral blood VIP, NPY and ET-1 had peaks and troughs (levels > 2SD from the mean) in both patients and controls, with approximate intervals of 10 min. Levels of CGRP showed little variation. The overall levels [median (range); pmol L-1] of VIP [patients 27 (2.1-85.5); controls 9.8 (0-34)] and NPY [patients 20 (0-110); controls 12 (5-19)] were higher in patients (P < 0.05). Circulating plasma levels of ET-1 and CGRP were about the same in both groups [ET-1: patients 18 (2-84); controls 18 (0-48); CGRP: patients 4 (1-18.5), controls 5.5 (1-15); P = NS]. Levels of CGRP, VIP and ET-1 were similar in the pulmonary and femoral arteries, whereas systemic arterial levels of NPY were higher than in the pulmonary artery.. The data demonstrate marked variability in circulating levels of the neuropeptides studied. In addition, peaks and troughs were observed every 10-15 min from all three vascular beds. If these peptides are secreted in a pulsatile pattern, then interpretations of single measurements should be guarded. Furthermore, this study raises interesting questions about the physiology of hormone secretion in man.

Topics: Aged; Calcitonin Gene-Related Peptide; Chronic Disease; Endothelin-1; Femoral Artery; Heart Failure; Humans; Middle Aged; Neuropeptide Y; Neuropeptides; Pulmonary Artery; Radioimmunoassay; Vasoactive Intestinal Peptide; Veins

Vasoactive intestinal peptide (VIP) is released both by neural endings and lymphocytes. Aim of our investigation was to study the effects of immunosuppressive therapy on VIP plasma concentrations. The research has been performed on 10 heart transplanted patients assuming cyclosporine (CYCL) and prednisone (PRED). The circulating T lymphocyte subsets, atrial natriuretic peptide (ANP), plasma renin activity (PRA), plasma aldosterone (PA) and plasma cortisol (PC) have been also assayed. Blood pressure (BP) and heart rate (HR) have been monitored over a 24-hour period to detect whether circulating VIP in heart transplanted patients is influenced by pharmacologically-induced interactions. Seriate samplings along the 24-hour span have been performed. Mean values of ANP, PRA and PA were increased, while VIP, PC and T lymphocyte subsets were decreased in heart transplanted patients as compared to clinically healthy subjects. ANOVA and Cosinor analysis showed, respectively, a statistically significant 24-hour variability and circadian rhythm for all the investigated variables only in normal subjects. BP and HR circadian rhythm in heart transplanted patients suggest that the adrenergic activity regulating the cardiovascular system is restored. This finding argues that the reduction in VIP plasma concentrations is likely due to the decreased lymphocyte production secondary to immunosuppressive therapy, or can also be ascribed to the inhibiting action of high circulating levels of ANP.

Topics: Adult; Aldosterone; Atrial Natriuretic Factor; Cardiomyopathy, Dilated; Circadian Rhythm; Female; Heart Failure; Heart Transplantation; Humans; Hydrocortisone; Immunosuppression Therapy; Male; Middle Aged; Postoperative Care; Renin; Vasoactive Intestinal Peptide

1. The effects of the angiotensin-converting enzyme (ACE) inhibitor lisinopril on plasma vasoactive intestinal polypeptides (VIP) and plasma noradrenaline, adrenaline and dopamine were studied in 12 patients with congestive heart failure over two consecutive 48-hr periods. The first day in each period served as a treatment day and the second as a control day. 2. A parallel monitoring was made of various hormonal parameters related to the renin-angiotensin-aldosterone system, and a right-heart catheter was used to monitor haemodynamics at rest. 3. Potent inhibition of the renin-system (as demonstrated by decreases in angiotensin converting enzyme (ACE) activity, angiotensin II and plasma aldosterone) together with improved haemodynamics (decreases in mean right atrial pressure, mean pulmonary arterial pressure, mean pulmonary capillary wedge pressure and mean systemic arterial pressure) were recorded. 4. Plasma VIP was significantly increased by a mean of 20.3% (P less than 0.01) on the lisinopril treatment days compared with the control days, whereas circulating catecholamines showed no significant pattern of change. 5. It is postulated that the potent vasodilatory neuromodulator VIP is implicated in the ACE inhibitor effects. 6. The ACE is a non-specific peptidase that previously has been implicated in the potentiation of other vasoactive endogenous systems (kinins and enkephalins).

Topics: Adult; Aged; Aldosterone; Angiotensin I; Angiotensin-Converting Enzyme Inhibitors; Catecholamines; Enalapril; Female; Heart Failure; Hemodynamics; Humans; Lisinopril; Male; Middle Aged; Renin; Vasoactive Intestinal Peptide

Topics: Adult; Aged; Female; Gastrointestinal Hormones; Glucagon; Heart Diseases; Heart Failure; Humans; Male; Middle Aged; Pancreatic Polypeptide; Shock; Vasoactive Intestinal Peptide