vasoactive-intestinal-peptide has been researched along with Hypoxia* in 31 studies
4 review(s) available for vasoactive-intestinal-peptide and Hypoxia
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Dipeptidyl peptidase 4 as a therapeutic target in ischemia/reperfusion injury.
Dipeptidyl peptidase 4 (DPP4, DPPIV, CD26, EC 3.4.14.5) was discovered more than four decades ago as a serine protease that cleaves off N-terminal dipeptides from peptide substrates. The development of potent DPP4 inhibitors during the past two decades has led to the identification of DPP4 as a target in the treatment of type 2 diabetes. The favorable effect of DPP4 inhibitors is based on prevention of the in vivo inactivation of the incretin hormone, glucagon-like peptide-1 (GLP-1) by DPP4. Apart from GLP-1, a number of other biologically active peptides are truncated by DPP4. For these peptides, the physiological relevance of their truncation has yet to be fully elucidated. Within the last 10years, DPP4 inhibitors have been employed in several animal models of lung and heart disease, in which injury was induced by an ischemic insult followed by subsequent reperfusion. In this review, we present a state-of-the-art of the ischemia/reperfusion injury (IRI)-related pharmacological actions of DPP4 substrates, including GLP-1, stromal cell-derived factor-1 alpha and vasoactive intestinal peptide. Furthermore, we discuss the large body of experimental work that now provides compelling evidence for the advantageous impact of DPP4 targeting in IRI. However, possible risks as well as underlying mechanisms are yet to be elucidated before translating these promising treatment strategies into clinical practice. Topics: Animals; Chemokine CXCL12; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Glucagon-Like Peptide 1; Humans; Hypoxia; Reperfusion Injury; Vasoactive Intestinal Peptide | 2012 |
Animal models of pulmonary arterial hypertension: the hope for etiological discovery and pharmacological cure.
At present, six groups of chronic pulmonary hypertension (PH) are described. Among these, group 1 (and 1') comprises a group of diverse diseases termed pulmonary arterial hypertension (PAH) that have several pathophysiological, histological, and prognostic features in common. PAH is a particularly severe and progressive form of PH that frequently leads to right heart failure and premature death. The diagnosis of PAH must include a series of defined clinical parameters, which extend beyond mere elevations in pulmonary arterial pressures and include precapillary PH, pulmonary hypertensive arteriopathy (usually with plexiform lesions), slow clinical onset (months or years), and a chronic time course (years) characterized by progressive deterioration. What appears to distinguish PAH from other forms of PH is the severity of the arteriopathy observed, the defining characteristic of which is "plexogenic arteriopathy." The pathogenesis of this arteriopathy remains unclear despite intense investigation in a variety of animal model systems. The most commonly used animal models ("classic" models) are rodents exposed to either hypoxia or monocrotaline. Newer models, which involve modification of classic approaches, have been developed that exhibit more severe PH and vascular lesions, which include neointimal proliferation and occlusion of small vessels. In addition, genetically manipulated mice have been generated that have provided insight into the role of specific molecules in the pulmonary hypertensive process. Unfortunately, at present, there is no perfect preclinical model that completely recapitulates human PAH. All models, however, have provided and will continue to provide invaluable insight into the numerous pathways that contribute to the development and maintenance of PH. Use of both classic and newly developed animal models will allow continued rigorous testing of new hypotheses regarding pathogenesis and treatment. This review highlights progress that has been made in animal modeling of this important human condition. Topics: Animals; Disease Models, Animal; Humans; Hypertension, Pulmonary; Hypoxia; Neprilysin; Vasoactive Intestinal Peptide | 2009 |
Hypoxic adaptation of the rat carotid body.
Three types of hypoxia with different levels of carbon dioxide (hypocapnic, isocapnic, and hypercapnic hypoxia) have been called systemic hypoxia. The systemic hypoxic carotid bodies were enlarged several fold, but the degree of enlargement was different for each. The mean short and long axes of hypocapnic and isocapnic hypoxic carotid bodies were 1.6 (short axis) and 1.8-1.9 (long axis) times larger than normoxic control carotid bodies, respectively. Those of hypercapnic hypoxic carotid bodies were 1.2 (short axis) and 1.5 (long axis) times larger than controls, respectively. The rate of enlargement in hypercapnic hypoxic carotid bodies was lower than in hypocapnic and isocapnic hypoxic carotid bodies. The rate of vascular enlargement in hypercapnic hypoxic carotid bodies was also smaller than in hypocapnic and isocapnic hypoxic carotid bodies. Thus, the enlargement of hypoxic carotid bodies is mainly due to vascular dilation. Different levels of arterial CO2 tension change the peptidergic innervation during chronically hypoxic exposure. The characteristic vascular arrangement was under the control of altered peptidergic innervation. During the course of hypoxic adaptation, the enlargement of the carotid bodies with vascular expansion began soon after the start of hypoxic exposure. During the course of recovery, the shrinking of the carotid bodies with vascular contraction also started at a relatively early period after the termination of chronic hypoxia. These processes during the course of hypoxic adaptation and during the course of recovery were under the control of peptidergic innervation. These findings may provide a standard for further studies of hypoxic carotid bodies. Topics: Adaptation, Physiological; Animals; Calcitonin Gene-Related Peptide; Carotid Body; Hypoxia; Neuropeptide Y; Rats; Substance P; Vasoactive Intestinal Peptide | 2005 |
[Vasoactive intestinal polypeptide (VIP)--possible importance in diseases of childhood].
Vasoactive intestinal peptide (VIP), first isolated from the gut, was originally considered a candidate gastrointestinal hormone. Since about 1975, however, it has become increasingly clear that it is primarily a neurotransmitter or neuromodulator and that it exerts its functions mainly by local release from nerve endings. VIP plays a hormonal role only when it is released in large amounts from a tumor, with a consequent overflow into the circulation and grossly elevated plasma concentrations of the peptide. Moderately increased VIP plasma and tissue concentrations that cause mainly local effects are found in intestinal ischemia. Crohn's disease and some other chronic inflammatory diseases of the bowel. VIP is also measured in increased amounts in the normal fetus and neonate, where it may play an important physiological role. Such an increase of VIP levels in the circulation could enhance perfusion and metabolic activity of tissues during their rapid-growth period. On the other hand, disorders with a disturbed VIP function such as achalasia and Hirschsprung's disease and possibly also asthma and cystic fibrosis seem to be characterized mainly by a derangement of smooth muscle activity and/or exocrine secretion. Considering this list of disorders where VIP has either a proven or suspected role, it is easy to imagine the significance of this peptide in pediatric pathophysiology. Topics: Asthma; Bronchodilator Agents; Celiac Disease; Child; Child, Preschool; Crohn Disease; Cystic Fibrosis; Digestive System; Esophageal Achalasia; Hirschsprung Disease; Humans; Hypoxia; Infant; Infant, Newborn; Placenta; Vasoactive Intestinal Peptide; Vipoma | 1985 |
1 trial(s) available for vasoactive-intestinal-peptide and Hypoxia
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Ventilatory effects of substance P, vasoactive intestinal peptide, and nitroprusside in humans.
Animal studies suggest that the neuropeptides, substance P and vasoactive intestinal peptide (VIP), may influence carotid body chemoreceptor activity and that substance P may take part in the carotid body response to hypoxia. The effects of these peptides on resting ventilation and on ventilatory responses to hypoxia and to hypercapnia have been investigated in six normal humans. Infusions of substance P (1 pmol.kg-1.min-1) and of VIP (6 pmol.kg-1.min-1) were compared with placebo and with nitroprusside (5 micrograms.kg-1.min-1) as a control for the hypotensive action of the peptides. Both peptides caused significantly less hypotension than nitroprusside. Substance P and nitroprusside caused significantly greater increases in ventilation and in the hypoxic ventilatory response than VIP. No changes were seen in hypercapnic sensitivity. The stimulation of ventilation and the differential effects on ventilatory chemosensitivity that accompanied hypotension are consistent either with stimulation of carotid body chemoreceptor activity or with an interaction with peripheral chemoreceptor input to the respiratory center, as is seen in animals. The similar cardiovascular but different ventilatory effects of the peptides suggest that substance P may also stimulate the carotid body in a manner independent of the effect of hypotension. This is consistent with a role of substance P in the hypoxic ventilatory response in humans. Topics: Adult; Blood Pressure; Carotid Body; Ferricyanides; Heart Rate; Humans; Hypercapnia; Hypoxia; Infusions, Intravenous; Male; Nitroprusside; Respiration; Substance P; Vasoactive Intestinal Peptide | 1990 |
26 other study(ies) available for vasoactive-intestinal-peptide and Hypoxia
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A negative trial for vasoactive intestinal peptide in COVID-19-associated acute hypoxaemic respiratory failure.
Topics: COVID-19; Humans; Hypoxia; Respiratory Insufficiency; Vasoactive Intestinal Peptide | 2023 |
Vasodilatory effect of the stable vasoactive intestinal peptide analog RO 25-1553 in murine and rat lungs.
Stable analogs of vasoactive intestinal peptide (VIP) have been proposed as novel line of therapy in chronic obstructive pulmonary disease (COPD) based on their bronchodilatory and anti-inflammatory effects. We speculated that VIP analogs may provide additional benefits in that they exert vasodilatory properties in the lung, and tested this hypothesis in both ex vivo and in vivo models.. In isolated perfused mouse lungs and in an in vivo rat model, pulmonary blood vessels were preconstricted by hypoxia and hemodynamic changes in response to systemic (ex vivo) or inhaled (in vivo) administration of the cyclic VIP analog RO 25-1553 were determined.. In mouse lungs, RO 25-1553 reduced intrinsic vascular resistance at normoxia, and attenuated the increase in pulmonary artery pressure in response to acute hypoxia. Consistently, inhalation of RO 25-1553 (1 mg · mL(-1) for 3 min) caused an extensive and sustained (> 60 min) inhibition of the pulmonary arterial pressure increase in response to hypoxia in vivo that was comparable to the effects of inhaled sildenafil. This effect was not attributable to systemic cardiovascular effects of RO 25-1553, but to a lung specific reduction in pulmonary vascular resistance, while cardiac output and systemic arterial hemodynamics remained unaffected. No adverse effects of RO 25-1553 inhalation on pulmonary gas exchange, ventilation-perfusion matching, or lung fluid content were detected.. Our findings demonstrate that inhaled delivery of the stable VIP analog RO 25-1553 induces a potent and sustained vasodilatory effect in the pulmonary circulation with no detectable adverse effects. Therapeutic inhalation of RO 25-1553 may provide vascular benefits in addition to its reported anti-inflammatory and bronchodilatory effects in COPD, yet caution is warranted given the overall poor results of vasodilator therapies for pulmonary hypertension secondary to COPD in a series of recent clinical trials. Topics: Administration, Inhalation; Animals; Hemodynamics; Hypoxia; Lung; Male; Mice; Peptides, Cyclic; Pulmonary Circulation; Rats; Receptors, Vasoactive Intestinal Peptide; Vasoactive Intestinal Peptide; Vasodilator Agents | 2013 |
17β-estradiol protects the lung against acute injury: possible mediation by vasoactive intestinal polypeptide.
Beyond their classical role as a class of female sex hormones, estrogens (e.g. 17β-estradiol) exert important biological actions, both protective and undesirable. We have investigated the ability of estradiol to protect the lung in three models of acute injury induced by 1) oxidant stress due to the herbicide paraquat; 2) excitotoxicity, caused by glutamate agonist N-methyl-d-aspartate; and 3) acute alveolar anoxia. We also assessed the role of estrogen receptors (ER) ERα and ERβ and the neuropeptide vasoactive intestinal peptide (VIP) in mediating this protection. Isolated guinea pig or rat lungs were perfused in situ at constant flow and mechanically ventilated. The onset and severity of lung injury were monitored by increases in pulmonary arterial and airway pressures, wet/dry lung weight ratio, and bronchoalveolar lavage fluid protein content. Estradiol was infused into the pulmonary circulation, beginning 10 min before induction of injury and continued for 60-90 min. Lung injury was marked by significant increases in the above measurements, with paraquat producing the most severe, and excitotoxicity the least severe, injury. Estradiol significantly attenuated the injury in each model. Both ER were constitutively expressed and immunohistochemically demonstrable in normal lung, and their selective agonists reduced anoxic injury, the only model in which they were tested. As it protected against injury, estradiol rapidly and significantly stimulated VIP mRNA expression in rat lung. Estradiol attenuated acute lung injury in three experimental models while stimulating VIP gene expression, a known mechanism of lung protection. The up-regulated VIP expression could have partially mediated the protection by estrogen. Topics: Animals; Estradiol; Guinea Pigs; Hypoxia; In Vitro Techniques; Lung; Lung Injury; Protective Agents; Pulmonary Circulation; Rats; Receptors, Estrogen; RNA, Messenger; Up-Regulation; Vasoactive Intestinal Peptide | 2011 |
Enhancement of pulmonary vascular remodelling and inflammatory genes with VIP gene deletion.
The pathogenesis of idiopathic pulmonary arterial hypertension (PAH) remains poorly understood. The present authors recently reported that mice with vasoactive intestinal peptide (VIP) gene disruption show a spontaneous phenotype of PAH, with pulmonary vascular remodelling and lung inflammation. To explore the underlying molecular mechanisms in this model, it was examined whether absence of the VIP gene might alter the expression of additional genes involved in the pathogenesis of PAH, as single-gene deletions, in the absence of hypoxia, rarely result in significant pulmonary vascular remodelling. Lung tissue from mice with targeted disruption of the vasoactive intestinal peptide gene (VIP(-/-) mice) and from control mice was subjected to whole-genome gene microarray analysis, and the results validated with quantitative, real-time PCR. Lungs from VIP(-/-) mice showed a wide range of significant gene expression alterations, including overexpression of genes that promote pulmonary vascular smooth muscle cell proliferation, underexpression of antiproliferative genes and upregulation of pro-inflammatory genes. In conclusion, vasoactive intestinal peptide is a pivotal modulator of genes controlling the pulmonary vasculature, its deficiency alone resulting in gene expression alterations that can readily explain both the vascular remodelling and associated inflammatory response in pulmonary arterial hypertension. The present findings shed more light on the molecular mechanisms of pulmonary arterial hypertension, and could lead to better understanding of the pathogenesis of human pulmonary arterial hypertension, and hence to improved therapy. Topics: Animals; Gene Deletion; Humans; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Hypoxia; Inflammation; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Oligonucleotide Array Sequence Analysis; Phenotype; Reverse Transcriptase Polymerase Chain Reaction; Vasoactive Intestinal Peptide | 2008 |
Morphological changes in the rat carotid body in acclimatization and deacclimatization to hypoxia.
Topics: Acclimatization; Animals; Calcitonin Gene-Related Peptide; Carotid Body; Chronic Disease; Hypoxia; Neuropeptide Y; Rats; Substance P; Time Factors; Vasoactive Intestinal Peptide | 2006 |
Effect of carbon dioxide on the structure of the carotid body: a comparison between normoxic and hypoxic conditions.
Topics: Animals; Calcitonin Gene-Related Peptide; Carbon Dioxide; Carotid Body; Chronic Disease; Hypercapnia; Hypocapnia; Hypoxia; Neuropeptide Y; Rats; Substance P; Time Factors; Vasoactive Intestinal Peptide; Vasodilation | 2006 |
Morphological changes in the rat carotid body 1, 2, 4, and 8 weeks after the termination of chronically hypocapnic hypoxia.
Morphological changes in the rat carotid bodies 1, 2, 4, and 8 weeks after the termination of chronically hypocapnic hypoxia (10% O2 for 8 weeks) were examined by means of morphometry and immunohistochemistry. The rat carotid bodies after 8 weeks of hypoxic exposure were enlarged several fold with vascular expansion. The carotid bodies 1 and 2 weeks after the termination of 8 weeks of hypoxic exposure were diminished in size, although their diameter remained larger than the normoxic controls. The expanded vasculature in chronically hypoxic carotid bodies returned to the normoxic control state. In the carotid bodies 1 week after the termination of chronic hypoxia, the density of NPY fibers was remarkably increased and that of VIP fibers was dramatically decreased in comparison with the density in chronically hypoxic carotid bodies. In the carotid bodies 2 and 4 weeks after the termination of hypoxia, the density of SP and CGRP fibers was gradually increased. In the carotid bodies 8 weeks after the termination of hypoxia, the appearance of the carotid body returned to a nearly normoxic state, and the density of SP, CGRP, VIP, and NPY fibers also recovered to that of normoxic controls. These results suggest that the morphological changes in the recovering carotid bodies start at a relatively early period after the termination of chronic hypoxia, and a part of these processes may be under the control of peptidergic innervation. Topics: Animals; Calcitonin Gene-Related Peptide; Carotid Body; Chronic Disease; Hypocapnia; Hypoxia; Immunohistochemistry; Nerve Fibers; Neuropeptide Y; Peptide Fragments; Rats; Rats, Wistar; Substance P; Time Factors; Vasoactive Intestinal Peptide | 2004 |
Peptidergic innervation in the rat carotid body after 2, 4, and 8 weeks of hypocapnic hypoxic exposure.
The distribution and abundance of neuropeptide-containing nerve fibers were examined in the carotid bodies of rats exposed to hypocapnic hypoxia (10% O2 in N2) for 2, 4, and 8 weeks. The carotid bodies after 2, 4, and 8 weeks of hypoxic exposure were enlarged by 1.2-1.5 times in the short axis, and 1.3-1.7 times in the long axis in comparison with the normoxic control ones. The enlarged carotid bodies contained a number of expanded blood vessels. Mean density per unit area (10(4) microm2) of substance P (SP) and calcitonin gene-related peptide (CGRP) immunoreactive fibers was transiently high in the carotid bodies after 4 weeks of hypoxic exposure, and decreased significantly to nearly or under 50% after 8 weeks of hypoxic exposure. Density of vasoactive intestinal polypeptide (VIP) immunoreactive fibers increased significantly in all periods of hypoxic exposure observed, and was especially high in the carotid bodies after 4 weeks of hypoxic exposure. Density of neuropeptide Y immunoreactive fibers was unchanged in the carotid bodies during hypoxic exposure. These characteristic changes in the density of SP, CGRP, and VIP fibers in the carotid bodies after 4 weeks of hypoxic exposure suggest that the role of these neuropeptide-containing fibers may be different in the carotid bodies after each of three periods of hypoxic exposure, and that the peptidergic innervation after 8 weeks of hypoxic exposure may show an acclimatizing state. Topics: Animals; Calcitonin Gene-Related Peptide; Carotid Body; Coloring Agents; Eosine Yellowish-(YS); Fluorescent Dyes; Hematoxylin; Hypocapnia; Hypoxia; Immunohistochemistry; Muscle, Smooth, Vascular; Nerve Fibers; Neuropeptide Y; Neuropeptides; Rats; Substance P; Time Factors; Vasoactive Intestinal Peptide | 2003 |
Rat carotid bodies in systemic hypoxia. Involvement of arterial CO2 tension in morphological changes.
Topics: Animals; Arteries; Calcitonin Gene-Related Peptide; Carbon Dioxide; Carotid Body; Hypercapnia; Hypoxia; Neuropeptide Y; Rats; Substance P; Vasoactive Intestinal Peptide | 2003 |
Relationship between vasoactive intestinal peptide and intrapulmonary vascular dilatation in children with various liver diseases.
To evaluate the potential of vasoactive intestinal peptide (VIP) as a pathogenic factor of intrapulmonary vascular dilatation (IVD) in hepatopulmonary syndrome (HPS).. HPS comprises a triad comprising liver dysfunction, IVD and hypoxaemia. Although the pathogenesis of the process has not been elucidated, many vasodilating substances, such as VIP, have been implicated in the development of pulmonary vascular abnormalities. IVD can be detected by contrast-enhanced echocardiography (CEE) before the development of abnormal gas exchange.. Forty-two children (20M, 22F; mean age 4.39 +/- 4.17 y) with various liver diseases who attended the paediatric liver clinic of King Chulalongkorn Memorial Hospital between March 2000 and February 2001 were recruited to the study. Each patient was tested for transcutaneous O2 saturation, CEE (applying the agitated normal saline technique), liver function test and serum VIP level.. Fourteen of the 42 patients (33%) were CEE positive. Only one of the 14 patients had associated hypoxia and clinical cyanosis. The serum VIP levels of children with liver disease were significantly higher than those of the controls (60.21 +/- 35.04 pg/ml vs 43.71 +/- 34.61 pg/ml, p = 0.03). CEE-positive children tended to have higher serum VIP levels than CEE-negative children (72.65 +/- 40.31 vs 53.99 +/- 31 pg/ml, p = 0.3). The serum VIP levels of biliary atresia (BA) patients with favourable outcomes (serum bilirubin < or = 34 micromol/L) were not significantly different from those with unfavourable outcomes (serum bilirubin > 34 micromol/L) (42.95 +/- 14.53 pg/ml vs 66.07 +/- 32.17 pg/ml, p = 0.5).. CEE is a non-invasive test for early detection of IVD in children with liver disease. VIP is not solely responsible for the pathogenesis of IVD in HPS. Further studies are required to determine which substances cause the development of IVD. Topics: Adolescent; Child; Child, Preschool; Dilatation, Pathologic; Echocardiography; Female; Hepatopulmonary Syndrome; Humans; Hypoxia; Infant; Male; Oxygen; Pulmonary Circulation; Vasoactive Intestinal Peptide | 2003 |
Depression of hypoxic arousal response in adolescent mice following antenatal vasoactive intestinal polypeptide blockade.
Late-gestation blockade of vasoactive intestinal polypeptide (VIP) activity in pregnant mice produces discrete morphological abnormalities in the somatosensory cortex of offspring. We investigated the functional implications of this lesion on the behavioural arousal response to moderate hypoxia. Pregnant mice received twice-daily injections of 200 microl saline (control), or saline + 50 microg VIP antagonist (anti-VIP) on embryonic days 17 and 18. Offspring were studied unrestrained at 6-7 weeks after birth, in a bias-flow whole-body plethysmograph during behavioural quiet sleep. Arousal was defined by movement (MVT) lasting > or =1 s. Hypoxic ventilatory (HVR) and arousal responses were measured during a 5 min exposure to 10 % O(2)-3 % CO(2) (hypoxia); peripheral chemoreflex drive was estimated by transient hyperoxia administered at rest and end-hypoxia (Dejours-type test). MVTs increased in all mice during hypoxia, but in anti-VIP mice: (a) MVT onset was delayed (174 +/- 90 vs. 108 +/- 59 s from the start of hypoxia, anti-VIP vs. control; P = 0.008); and (b) MVTs were less frequent, and total MVT time in hypoxia was less (8 +/- 7 vs. 15 +/- 9 %; P = 0.03). The HVR, and peripheral drive at rest and end-hypoxia were comparable in control and anti-VIP mice. In conclusion, a significant arousal deficit was evident in anti-VIP mice. This was not associated with obviously deranged peripheral or brainstem-mediated responses to hypoxia during sleep. This may signal a general deficit in the way hypoxic distress is monitored and processed, and arousal initiated and sustained in these mice. Topics: Animals; Arousal; Female; Hyperoxia; Hypoxia; Male; Mice; Plethysmography; Pregnancy; Prenatal Exposure Delayed Effects; Respiratory Mechanics; Sleep; Tidal Volume; Vasoactive Intestinal Peptide | 2002 |
Vasoactive intestinal peptide protects guinea-pig detrusor nerves from anoxia/glucopenia injury.
Vasoactive intestinal peptide (VIP) was tested for its capability to protect the intrinsic nerves of guinea-pig urinary bladder from damage due to anoxia/glucopenia and reperfusion. Guinea-pig detrusor strips were mounted for tension recording in small organ baths and the nerves were subjected to electric field stimulation. VIP (0.3 microM) improved significantly the response of strips to electrical field stimulation either during anoxia/glucopenia or thereafter during reperfusion, as compared to untreated tissues. The antioxidant activity of VIP assessed as its capability to scavenge peroxyl radicals during linoleic acid oxidation corresponded to 6.42+/-0.13 pIC(50) M, i.e. close to the concentration proved to protect strips against the anoxic--glucopenic and reperfusion damage. Topics: Animals; Dose-Response Relationship, Drug; Electric Stimulation; Female; Free Radical Scavengers; Glucose; Guinea Pigs; Hypoxia; In Vitro Techniques; Lipid Peroxidation; Male; Muscle Contraction; Muscle, Smooth; Peroxides; Reperfusion Injury; Urinary Bladder; Vasoactive Intestinal Peptide | 2001 |
Morphological adaptation of the peptidergic innervation to chronic hypoxia in the rat carotid body.
Topics: Adaptation, Physiological; Animals; Calcitonin Gene-Related Peptide; Carotid Body; Hypoxia; Immunohistochemistry; Nerve Fibers; Neuropeptide Y; Neuropeptides; Oxygen; Rats; Substance P; Vasoactive Intestinal Peptide | 2000 |
Changes in the peptidergic innervation of the rat carotid body a month after the termination of chronic hypoxia.
Topics: Animals; Calcitonin Gene-Related Peptide; Carotid Body; Chronic Disease; Hypoxia; Immunohistochemistry; Neuropeptide Y; Neuropeptides; Rats; Substance P; Time Factors; Vasoactive Intestinal Peptide | 2000 |
Plasticity in the phenotypic expression of catecholamines and vasoactive intestinal peptide in adult rat superior cervical and stellate ganglia after long-term hypoxia in vivo.
Sympathetic ganglia in the adult rat contain various populations of nerve cells which demonstrate plasticity with respect to their transmitter phenotype. The plasticity of the neuronal cell bodies and of the small intensely fluorescent cells in the superior cervical and stellate ganglia in response to hypoxia in vivo (10% O2 for seven days) was assessed by studying the expression of catecholamines and vasoactive intestinal peptide. The levels of norepinephrine, dopamine, 3,4-dihydroxyphenylacetic acid and vasoactive intestinal peptide immunoreactivity were determined. In addition, the density of the immunohistochemical staining of cells for tyrosine hydroxylase and vasoactive intestinal peptide was evaluated. In the intact superior cervical ganglion, hypoxia increased the dopamine level as well as the density of small intensely fluorescent cells immunolabelled for tyrosine hydroxylase and vasoactive intestinal peptide. In the axotomized ganglion, hypoxia elicited a twofold rise in the level of the vasoactive intestinal peptide as well as enhancing the density of neuronal cell bodies immunostained for this peptide. Thus, the effect of hypoxia on the expression of vasoactive intestinal peptide expression in neurons was dependent on neural interactions. In the intact stellate ganglion, hypoxia alone induced a 1.5-fold increase in the density of neuronal cell bodies immunostained for vasoactive intestinal peptide. Thus, ganglia-specific factors appeared to play a role in determining changes in neuronal phenotype in response to hypoxia. The present study provides evidence for the involvement of dopamine and vasoactive intestinal peptide in ganglionic responses to long-term hypoxia as well as for differential responses by the two ganglionic cell populations, i.e. neuronal cell bodies and small intensely fluorescent cells. Changes in the expression of the vasoactive intestinal peptide during long-term hypoxia may be of energetic, trophic and/or synaptic significance. Hypoxia may be considered to be a vasoactive intestinal peptide-inducing factor in sympathetic ganglia. Topics: Animals; Catecholamines; Chronic Disease; Hypoxia; Immunohistochemistry; Male; Neuronal Plasticity; Phenotype; Rats; Rats, Sprague-Dawley; Reference Values; Stellate Ganglion; Superior Cervical Ganglion; Tyrosine 3-Monooxygenase; Vasoactive Intestinal Peptide | 1999 |
Altered daily rhythms of brain and pituitary indolamines and neuropeptides in long-term hypoxic rats.
To determine whether sustained hypoxia alters daily rhythms in brain and pituitary neurotransmitters, the daily variations in vasoactive intestinal peptide-like immunoreactivity (VIP-LI), neuropeptide Y-like immunoreactivity (NPY-LI), serotonin (5-HT), and 5-hydroxyindole-3-acetic acid (5-HIAA) content were determined in discrete brain regions, pineal gland and anterior pituitary of hypoxic (10% O(2); 14 days) and normoxic rats. Hypoxia suppressed daily variations in VIP-LI in the suprachiasmatic nuclei (SCN) and the anterior pituitary, enhanced the daily rhythmicity in serotonergic elements of the caudal part of the dorsomedial medulla oblongata (DMMc), and even induced daily variations in NPY-LI in the DMMc as well as in the ventrolateral medulla oblongata. In addition, punctual alterations in the rhythmicity of 5-HT and 5-HIAA in the pineal gland and of plasma corticosterone were observed in hypoxic rats. Thus results of this study indicate that a permanent nonphotic stimulus, such as sustained hypoxia, may affect the functioning of the internal clock located in the SCN and may alter the daily rhythmicity in neurotransmitter content of some brain nuclei and the pituitary gland. Topics: Animals; Brain; Brain Chemistry; Circadian Rhythm; Hydroxyindoleacetic Acid; Hypoxia; Male; Neuropeptide Y; Pituitary Gland; Rats; Serotonin; Time Factors; Vasoactive Intestinal Peptide | 1999 |
Protection against developmental deficiencies by a lipophilic VIP analogue.
Stearyl-Nle-VIP (SNV) is a novel agonist of vasoactive intestinal peptide (VIP) exhibiting a 100-fold greater potency than the parent molecule and specificity for a receptor associated with neuronal survival. Here, the developmental and protective effects of SNV were investigated in vivo using two models of developmental retardation, hypoxia and cholinergic blockade. In both cases chronic administration of SNV during development provided protective effects. Water maze experiments on the weaned animals have demonstrated a prophylactic action for SNV and enhancement of spatial memory in animals exposed to a cholinotoxin. SNV may act by providing neuroprotection, thereby improving cognitive functions. This work is dedicated to Prof. R.J. Wurtman whose inspiration and leadership in the field of neuroscience and cognition is beyond comparison. Topics: Aging; Animals; Aziridines; Choline; Hypoxia; Intellectual Disability; Male; Maze Learning; Memory; Neuromuscular Blocking Agents; Neurotoxins; Rats; Space Perception; Vasoactive Intestinal Peptide | 1998 |
Relaxant effects of vasoactive intestinal peptide on pulmonary artery in chronically hypoxic rats.
The object of this study is to investigate the effect of VIP on pulmonary artery of chronically hypoxic rats. It was shown that chronic hypoxia depressed significantly pulmonary artery relaxation induced by VIP as compared with those of control (P < 0.001). The vascular relaxation of both groups was correlated with concentration of VIP. In addition, the relaxant effect of VIP on pulmonary arteries in rats was endothelium-independent, and was not prevented by indomethacin or nordihydroguaiaretic acid, but was abolished completely by methylene blue. These results suggest that the lower relaxation of pulmonary artery in rats might not be due to the endothelial injury caused by chronic hypoxia, and chronic hypoxia may inhibit directly the soluble guanylate cyclase in vascular smooth muscle cells involved in synthesis of cGMP and thus reduced the sensitivity and reactivity of pulmonary artery to VIP. Topics: Animals; Cyclooxygenase Inhibitors; Guanylate Cyclase; Hypoxia; Indomethacin; Male; Masoprocol; Methylene Blue; Muscle Relaxation; Muscle, Smooth, Vascular; Pulmonary Artery; Rats; Rats, Wistar; Vasoactive Intestinal Peptide | 1996 |
Chronic hypoxia affects peripheral and central vasoactive intestinal peptide-like immunoreactivity in the rat.
The influence of long-term hypoxia on vasoactive intestinal peptide-like immunoreactivity (VIP-LI) in discrete brain areas and peripheral structures was assessed by RIA. Rats were exposed to normobaric hypoxia (10% O2-90% N2) for 14 days. VIP-LI was significantly increased in carotid bodies of hypoxic animals (204% vs. normoxic animals). On the other hand, VIP-LI was decreased in the anterior pituitary (-68%), suprachiasmatic nuclei (-29%) and periventricular nuclei (-26%). No significant variation in VIP-LI was observed in other peripheral structures and discrete brain area studied. These results suggest that long-term hypoxia induces alterations in VIP systems implicated in chemoreception, biological rhythms and neuroendocrine functions. Topics: Animals; Brain; Carotid Body; Chronic Disease; Ganglia; Hypoxia; Male; Organ Specificity; Pituitary Gland, Anterior; Radioimmunoassay; Rats; Rats, Inbred Strains; Reference Values; Vasoactive Intestinal Peptide | 1994 |
Bicarbonate transport by rabbit duodenum in vitro: effect of vasoactive intestinal polypeptide, prostaglandin E2, and cyclic adenosine monophosphate.
Duodenal surface cells secrete bicarbonate that provides a barrier against injury. The current experiments were performed to identify duodenal bicarbonate regulatory and transport pathways.. Rabbit proximal duodenal mucosa were mounted in chambers under short-circuited conditions. Bicarbonate transport, short-circuit current (Isc), and potential difference (PD) were quantitated in response to prostaglandin E2 (PGE2), vasoactive intestinal polypeptide (VIP), and dibutyryl cyclic adenosine monophosphate (db-cAMP). Anoxia (N2), 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and Cl(-)-free solutions, ouabain, and Na-free solutions were also studied, as was the effect of VIP and PGE2 on duodenocyte cAMP.. PGE2, VIP, db-cAMP, and theophylline significantly increased bicarbonate secretion, Isc, and PD. Ouabain, Na(+)-free bathing solutions, and anoxia (N2) inhibited the responses. DIDS and Cl(-)-free solutions abolished the PGE2-induced response, reduced the response to VIP by about 50%, and had no effect on the response to db-cAMP. After PGE2 and VIP, cAMP concentration increased, yet was likely independent of bicarbonate secretion.. Mammalian duodenal HCO3- transport requires Na+, Na+/K(+)-adenosine triphosphatase and O2-dependent metabolic pathways and is stimulated by PGE2, VIP, and cAMP, acting by distinct pathways. Topics: 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; Animals; Bicarbonates; Bucladesine; Chlorides; Cyclic AMP; Dinoprostone; Duodenum; Hypoxia; In Vitro Techniques; Intestinal Mucosa; Ion Transport; Male; Ouabain; Rabbits; Sodium; Vasoactive Intestinal Peptide | 1993 |
[The relation of vasoactive intestinal peptide and acute hypoxia].
In order to observe the effect of acute hypoxia on release of vasoactive intestinal peptide (VIP), the plasma VIP content was determined in anesthetized dogs by a specific radioimmunoassay technique during acute hypoxia. Blood gases and hemodynamics were monitored simultaneously. After inhalation of 10% oxygen. the plasma VIP levels elevated along with decrease in PaO2 and increase in pulmonary artery pressure. The plasma concentration of VIP in the portal vein increased significantly from 106 +/- 21 pg/ml before hypoxia to 173 +/- 36 pg/ml 15 minutes after the onset of hypoxia (P less than 0.01). The difference of arterio-venous VIP content increased from -3 +/- 6 pg/ml before hypoxia to +9 +/- 7 pg/ml after inhalation of 10% oxygen for 30 minutes. The results suggested that VIP was released from the gastrointestinal tract as well as from the lung in case of hypoxia and pulmonary hypertension. It is considered that the release of VIP may be an adaptive and compensatory response, promoting vasodilation and perfusion in vital organs. Topics: Animals; Dogs; Female; Hypertension, Pulmonary; Hypoxia; Male; Radioimmunoassay; Vasoactive Intestinal Peptide | 1990 |
Reduced systolic blood pressure elevations during maximum exercise at simulated altitudes.
Ten healthy female subjects performed maximum exercise on a bicycle in an altitude chamber during normoxia and hypobaric hypoxia simulating altitudes of 2,450, 3,700 and 4,600 m. The increases in systolic blood pressure responses were reduced with the degree of hypobaric hypoxia, whereas heart rate and diastolic pressure responses were unchanged. The increases in blood levels of aldosterone, plasma renin activity, adrenaline, noradrenaline, neuropeptide-Y and vasoactive intestinal peptide were similar at the different simulated altitudes. Angiotensin-converting enzyme and vasoactive intestinal peptide levels were not affected by hypoxia or maximum exercise. The present results suggest that the decreases in systolic blood pressure responses during hypobaric hypoxia could not be explained by altered responses of the measured vasoactive substances from the renin-angiotensin, gastrointestinal, and autonomic nervous systems. Topics: Adult; Altitude; Atmosphere Exposure Chambers; Blood Pressure; Catecholamines; Exercise; Female; Humans; Hypoxia; Lactates; Lactic Acid; Neuropeptide Y; Oxygen Consumption; Peptidyl-Dipeptidase A; Physical Endurance; Renin-Angiotensin System; Vasoactive Intestinal Peptide | 1989 |
Vasoactive intestinal polypeptide potentiates the hypoxemia-induced decrease in splanchnic circulation in the rat.
The effects of acute infusion of vasoactive intestinal polypeptide (VIP) and hypoxemia on splanchnic circulation were examined in 35 awake Sprague-Dawley rats. Indwelling catheters were placed in the superior vena cava and the proximal aorta via the internal jugular vein and internal carotid artery, respectively, while the rats were under ether anesthesia. Four hours later, when the rats were awake and active, VIP (molecular lot 3226) was infused intraarterially for 30 minutes. The distribution of cardiac output was measured at the end of VIP infusion using 125I-labeled microspheres. VIP was administered at a low (1.5 ng/min) and a high infusion rate (44.1 ng/min) for 30 minutes. The effect of hypoxemia on circulatory response to VIP was examined only in the high VIP infusion group, by placing the rat in a 10% oxygen environment. Appropriate control experiments were performed with each group. The high-dose VIP resulted in a marked reduction in distribution of cardiac output to the splanchnic circulation. This effect was potentiated by hypoxemia, particularly in the distal ileum and colon. The metabolic clearance rate of VIP increased with the rate of VIP infusion and was decreased by hypoxemia. It was concluded that only in high concentration does VIP have any effect on splanchnic circulation. However, in the presence of hypoxemia, VIP may have an important role in cardiovascular compensatory response and may contribute to the development of ischemic bowel injury. Topics: Animals; Cardiac Output; Hypoxia; Metabolic Clearance Rate; Rats; Rats, Inbred Strains; Splanchnic Circulation; Vasoactive Intestinal Peptide | 1988 |
Pulmonary vascular effects of vasoactive intestinal peptide in conscious newborn lambs.
Vasoactive intestinal peptide (VIP) may be a neurotransmitter in a peptidergic nervous system and is found in nerves in pulmonary blood vessels. Information regarding its pulmonary vascular effects is limited. We therefore studied VIP's effect on pulmonary vascular tone in the immature lung. Normoxic and hypoxic unsedated newborn lambs with chronically implanted flow probes around the right and left pulmonary arteries were used. VIP was injected into one pulmonary artery only, and direct effects of this peptide on the pulmonary vessels were determined by comparing the flow changes in the injected vs. the uninjected lung. VIP was a powerful pulmonary vasodilator with a threshold of 0.3 microgram/kg. It also was a systemic vasodilator (after 1 microgram/kg, aortic pressure fell 27% and cardiac output increased 29%, both P less than 0.01), with a threshold of 0.1 microgram/kg. Pretreatment with propranolol (1 mg/kg iv) did not abolish pulmonary or systemic vasodilation after VIP. On the other hand, pretreatment with indomethacin (3 mg/kg per day for 3 days) abolished VIP-induced pulmonary vasodilation but probably did not affect systemic vasodilation. We conclude that VIP is a powerful pulmonary vasodilator in the newborn lamb and that this dilation can be blocked by the cyclooxygenase inhibitor indomethacin. VIP is also a powerful systemic vasodilator in the newborn lamb but this effect is not blocked by either propranolol or indomethacin. Topics: Animals; Animals, Newborn; Blood Vessels; Consciousness; Female; Gases; Hemodynamics; Hypoxia; Indomethacin; Male; Propranolol; Pulmonary Circulation; Sheep; Vasoactive Intestinal Peptide | 1984 |
Vasoactive intestinal polypeptide and the canine cerebral circulation.
A potential role for cerebrovascular nerves containing vasoactive intestinal polypeptide (VIP) was examined in 24 anesthetized, ventilated dogs. Cerebral blood flow (CBF) was measured by either the cerebral venous outflow or microsphere method. Plasma VIP concentration was measured by radioimmunoassay. Hypercapnia (5% and 10% CO2) and hypoxia (7% O2) produced significant increases in cerebral venous outflow, but had no affect on arterial or cerebral venous VIP concentrations. Measurements of VIP in cerebrospinal fluid (CSF) made during 5% and 8% CO2 breathing also were not different from control values. VIP produced large dose-dependent increases in common carotid artery and temporalis muscle blood flow when injected or infused intraarterially; however, VIP had no effect on total or regional cerebral blood flow (rCBF) within the brain when administered in a similar manner. Unilateral perfusion of the cerebral ventricles with VIP produced significant increases (range: 11-80%) in rCBF. These data are consistent with the possibility that local release of VIP from perivascular nerve endings could affect CBF. The unresponsiveness of canine cerebral vessels to blood-borne VIP may be due to the blood-brain barrier, since VIP dilates cerebral vessels when the barrier is bypassed by intraventricular infusion. These studies do not support the hypothesis that CBF changes induced during hypercapnia or hypoxia are mediated by VIP. Topics: Animals; Arteries; Cerebrovascular Circulation; Dogs; Female; Gastrointestinal Hormones; Head; Hypercapnia; Hypoxia; Injections, Intraventricular; Male; Vasoactive Intestinal Peptide | 1981 |
[Release of vasoactive intestinal polypeptide during acute hypoxia and acute respiratory acidosis (author's transl)].
Topics: Acidosis, Respiratory; Acute Disease; Animals; Dogs; Gastrointestinal Hormones; Hypoxia; Lung; Vasoactive Intestinal Peptide | 1980 |