neuropeptide-y and Pulmonary-Edema

The seriousness of scorpion envenomation results essentially from left cardiac function with pulmonary oedema and/or a state of shock. Adrenergic myocarditis, toxic myocarditis and myocardial ischemia are the 3 mechanisms that explain the cardiac dysfunction. Myocardial ischemia is not only due to the release of catecolamines but also the effect of the cytokines and/or neuropeptide Y on the coronary vessels. The cardiac damage can be due or enhanced by the depressive effect of the cytokines on the myocardial cells. The frequently observed hyperglycaemia only enhances the state of the already damaged myocardium.

Topics: Acidosis; Animals; beta-Thromboglobulin; Blood Platelets; Catecholamines; Cytokines; Endothelin-1; Humans; Hyperglycemia; Myocardial Ischemia; Myocarditis; Myocardium; Neuropeptide Y; Pulmonary Edema; Scorpion Stings; Scorpion Venoms; Scorpions; Shock, Cardiogenic; Stress, Physiological

The present study was undertaken to evaluate roles of nitric oxide in the central nervous system in the development of neurogenic pulmonary edema. Nitric oxide donor compounds have been reported to be effective for controlling some kinds of pulmonary edema.. Randomized trial.. Experimental university pharmacology laboratory.. Wistar rats anesthetized with pentobarbital.. Neurogenic pulmonary edema was induced by injections of fibrinogen and thrombin into the cisterna magna. Physiologic roles of nitric oxide were evaluated by using NG-nitro-l-arginine methyl ester (a nitric oxide synthase inhibitor) or l-arginine (a nitric oxide donor compound). Vagus nerves were either left intact or bilaterally severed 20 mins before the injections of fibrinogen and thrombin.. Because enhanced sympathetic nerve activity mediates neurogenic pulmonary edema, the concentration of neuropeptide Y, a neurotransmitter, in edema fluid was measured by using enzyme-linked immunosorbent assay. To evaluate the severity of pulmonary edema and pulmonary vascular permeability, lung water content and protein concentration in edema fluid were analyzed. In rats with intact vagus nerves, injection of NG-nitro-l-arginine methyl ester into the cisterna magna worsened the pulmonary edema, whereas l-arginine had no effect. In contrast, in vagotomized rats, l-arginine abrogated pulmonary edema, whereas NG-nitro-l-arginine methyl ester exerted no influence. Likewise, the ratio of edema fluid protein to serum protein and the neuropeptide Y concentration were increased by NG-nitro-l-arginine methyl ester in rats with the vagus nerves intact and were diminished by l-arginine in vagotomized rats.. Neurogenic pulmonary edema is characterized by elevated pulmonary vascular permeability and may be inhibited by nitric oxide production in the medulla oblongata.

Topics: Analysis of Variance; Animals; Arginine; Body Water; Enzyme-Linked Immunosorbent Assay; Medulla Oblongata; Neuropeptide Y; NG-Nitroarginine Methyl Ester; Nitric Oxide; Proteins; Pulmonary Edema; Rats; Rats, Wistar; Vagus Nerve

Increased intracranial pressure induces neurogenic pulmonary edema (NPE), potentially explaining why only lungs from less than 20% of brain dead organ donors can be used for transplantation. This study investigated the underlying mechanisms of NPE, focusing on neuropeptides, which potently induce vasoconstriction, vasodilatation, and neurogenic inflammation.. Brain death was induced in 10 pigs by increasing the intracranial pressure. Eight additional pigs served as controls. Neuropeptide Y (NPY), calcitonin gene-related peptide (CGRP), and substance P were analyzed in plasma, bronchoalveolar lavage (BAL) fluid, and homogenized lung tissue 6 hours after brain death. Pulmonary oxygen exchange was estimated using partial pressure of arterial oxygen (Pao2)/fraction of inspired oxygen (Fio2), and pulmonary edema by wet/dry weight ratio.. Brain death induced a decrease in Pao(2)/Fio2 (p < 0.001) and increased the wet/dry weight of both apical (p = 0.01) and basal lobes (p = 0.03). NPY and CGRP concentrations were higher in the BAL fluid of brain-dead animals compared with controls (p = 0.02 and p = 0.02) and were positively correlated with the wet/dry weight ratio. NPY content in lung tissue was lower in brain-dead animals compared with controls (p = 0.04) and was negatively correlated with the wet/dry weight ratio. There were no differences in substance P concentrations between the groups.. NPY was released from the lung tissue of brain-dead pigs, and its concentration was related to the extent of pulmonary edema. NPY may be one of several crucial mediators of neurogenic pulmonary edema, raising the possibility of treatment with NPY-antagonists to increase the number of available lung donors.

Topics: Animals; Biomarkers; Brain Death; Bronchoalveolar Lavage Fluid; Calcitonin Gene-Related Peptide; Disease Models, Animal; Female; Lung; Neurogenic Inflammation; Neuropeptide Y; Neuropeptides; Predictive Value of Tests; Pulmonary Edema; Substance P; Swine; Vasoconstriction; Vasodilation

In order to find some treatments for respiratory failure caused by pulmonary edema, we investigated the mechanism of neurogenic pulmonary edema. Previously, stimulation of sympathetic nerves caused an increase in pulmonary vascular permeability, possibly due to neuropeptide Y. Neuropeptide Y injected into the trachea increased lung vascular permeability dose-dependently, the ED50 of which was 0.3-1 nM. Such an effect remained even after treatment with reserpine, as well as in the presence of alpha- and beta-blockers. And norepinephrine enhanced the effect of neuropeptide Y on lung vascular permeability. These responses were almost similar to those obtained by stimulation of sympathetic nerves. Furthermore, neuropeptide Y, in fibrin-induced pulmonary edema, was localized in alveolar macrophages and alveolar spaces, amounting to approximately 200 nM in edema fluid. The value was significantly greater than that obtained in hydrostatic pulmonary edema by 10-30 times. Peptide YY, an analogue of neuropeptide Y, had no action on lung vascular permeability, whereas the effect of neuropeptide Y was inhibited by pretreatment with neuropeptide Y- 13-36, an antagonist for Y3-recetor subtype. These results suggested that neuropeptide Y enhances the lung vascular permeability via Y3-recetor subtype. Neuropeptide Y- 13-36, in fibrin-induced pulmonary edema, decreased a ratio of protein concentration in edema fluid to that in serum, indicating that neuropeptide Y actually acts a role in the development of neurogenic pulmonary edema, via an increase in lung vascular permeability.

Topics: Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Adrenergic Uptake Inhibitors; Animals; Capillary Permeability; Dose-Response Relationship, Drug; Fibrin; Neuropeptide Y; Norepinephrine; Peptide YY; Pulmonary Circulation; Pulmonary Edema; Rats; Receptors, Neuropeptide; Reserpine; Respiratory Insufficiency

Tropospheric ozone exerts well-described toxic effects on the respiratory tract. Less documented, by contrast, is the ability of ozone to induce protective mechanisms against agents that are toxic to the lungs. In particular, interactions between ozone and the sympathetic nervous system have never been considered. Using a model of permeability edema in isolated perfused rabbit lungs, we report here that, immediately after exposure of rabbits to 0.4 ppm ozone for 4 hr, the pulmonary microvascular responses to acetylcholine and substance P are completely blocked. Several lines of evidence, including partial inhibition of the ozone-induced protective effect by several drugs (alpha2- and beta-adrenergic antagonists, neuropeptide Y antagonist, guanethidine), measured levels of released catecholamines in blood and urine and the in vitro response of isolated lungs exposed to 0.4 ppm ozone all seem to suggest that ozone can stimulate pulmonary adrenergic fibers and induce the local release of catecholamines and neuropeptide Y, this resulting in transient protection against pulmonary edema. We also showed that, 48 hr after the exposure, ozone increased the baseline microvascular permeability and the response to low concentrations of acetylcholine.

Topics: Acetylcholine; Adrenergic Agents; Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Animals; Capillary Permeability; Catecholamines; Dose-Response Relationship, Drug; Female; Guanethidine; Lung; Male; Microscopy, Electron; Nerve Fibers; Neuropeptide Y; Ozone; Pulmonary Edema; Pulmonary Wedge Pressure; Rabbits; Substance P; Time Factors

The effect of neuropeptide Y on the number of perivascular carbon deposits, assessed as a measure of lung vascular permeability, was examined in isolated perfused lung preparations of rats. The number of carbon particle deposits after bronchial application of neuropeptide Y was increased in a dose-dependent manner. In the presence of a beta-adrenoceptor antagonist, norepinephrine augmented the effects of neuropeptide Y. Peptide YY, an analog of neuropeptide Y, demonstrated a much lower potency for increasing the number of carbon deposits, and neuropeptide Y-(18-36), which elicits a weak antagonist action on the neuropeptide Y Y3 receptor, significantly decreased the neuropeptide Y-induced increase. Furthermore, examination of the influence of neuropeptide Y-(18-36) pretreatment on fibrin-induced neurogenic pulmonary edema, in rats, revealed a reduction of the protein concentration ratio of tracheal fluid to serum. Therefore, we conclude that neuropeptide Y may elevate vascular permeability in the pulmonary circulation, conceivably through the neuropeptide Y Y3 receptor, and that neuropeptide Y may in fact play a physiological role even in the in-situ pulmonary circulation.

Topics: Animals; Capillary Permeability; Carbon; Male; Neuropeptide Y; Norepinephrine; Propranolol; Pulmonary Edema; Pyrilamine; Rats; Rats, Wistar; Receptors, Neuropeptide Y

1. The modulatory role of neuropeptide Y (NPY) on pulmonary oedema induced by acetylcholine and capsaicin was investigated. The effects of NPY on the haemodynamic response to acetylcholine, phenylephrine and substance P were also investigated. 2. Isolated, ventilated, exsanguinated lungs of the rabbit were perfused with a constant flow of recirculating blood-free perfusate. The double/arterial/venous occlusion method was used to partition the total pressure gradient (delta Pt) into four components: the arterial gradient (delta Pa), the pre- and post-capillary gradients (respectively delta Pa' and delta Pv') and the venous pressure gradient (delta Pv). Endothelial permeability was evaluated by measuring the capillary filtration coefficient (Kf,c). 3. Acetylcholine (10(-8) M to 10(-4) M) and substance P (SP, 10(-10) M to 10(-6) M) induced a concentration-dependent increase in the Kf,c. Capsaicin (10(-4) M) and 5-hydroxytryptamine (5-HT) (10(-4) M) also increased this parameter. NPY (10(-8) M) completely inhibited the effects of acetylcholine and capsaicin on the Kf,c, without preventing the effects of substance P and 5-HT. 4. Acetylcholine induced concentration-dependent vasoconstriction in the precapillary segment. The effect was inhibited by NPY and aspirin, an inhibitor of cyclo-oxygenase, while ketanserin, a 5-HT2 receptor antagonist, and SR140333, a new NK1 antagonist, had no protective effect. Phenylephrine increased delta Pa at high concentration, an effect also inhibited by NPY and aspirin. Substance P had no significant haemodynamic effect. When injected together with NPY, substance P (10(-6) M) induced a significant increase in the total pressure gradient. 5. It was concluded that NPY can protect the lung against acetylcholine- and capsaicin-induced oedemavia a prejunctional modulatory effect on the C-fibres. NPY also inhibits acetylcholine-evoked precapillary and phenylephrine-induced arterial vasoconstriction, probably by interfering with cyclo-oxygenase products synthesis.

Topics: Acetylcholine; Animals; Capsaicin; Female; Hemodynamics; Male; Neuropeptide Y; Perfusion; Permeability; Pulmonary Edema; Rabbits; Serotonin; Substance P; Vasoconstriction

STUDY OBJECTIVE - The aim of the study was to measure plasma neuropeptide Y, which is related to sympathetic nerve stimulation, in patients admitted to a coronary care unit and to relate the findings to clinical information. DESIGN - Plasma neuropeptide Y was measured on admission and the results were related to the cause of admission and to clinical information collected prospectively and retrospectively. SUBJECTS - Plasma subjects were obtained from 377 consecutive daytime admissions to the coronary care unit at Södersjukhuset. Results of only the first sample in each patient are included in this study, so 45 cases observed more than once (readmitted patients) were omitted. Six samples were abandoned because of technical failures. The study therefore comprises 326 patients. Clinical diagnoses were defined as acute myocardial infarction, arrhythmia, angina pectoris, and miscellaneous (all other diagnoses). Heart failure was defined according to a modified Killip scheme. MEASUREMENTS and RESULTS - Neuropeptide Y like immunoreactivity was measured by radio-immunoassay. Plasma concentrations above normal (greater than 30 pmol.litre-1) were found in association with: increased age, female sex, diuretic treatment, tachycardia, arterial hypotension, increased respiratory rate, and mortality in the unit. There was a strong relationship between high neuropeptide Y concentrations and: moderate left heart failure (63%), pulmonary oedema (90%), and cardiogenic shock (100%). Of patients without heart failure only 25% had raised neuropeptide Y. In multivariate analysis, the severity of heart failure (Killip class), heart rate and respiratory rate were the only variables that were significantly and independently related to plasma neuropeptide Y. CONCLUSIONS - The presence and degree of circulatory disturbance, in particular tachycardia and left heart failure, were strongly related to increased plasma concentrations of neuropeptide Y in coronary care patients.

Topics: Aged; Aged, 80 and over; Angina Pectoris; Arrhythmias, Cardiac; Coronary Care Units; Diuretics; Epinephrine; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Neuropeptide Y; Norepinephrine; Pilot Projects; Pulmonary Edema; Risk Factors; Shock, Cardiogenic