Plasma Levels Of Vasoactive Intestinal Peptide Research Articles

Plasma levels of VIP are not elevated during PACAP- and VIP-induced cluster headache attacks: an exploratory study.

Pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP) provoked cluster headache attacks in individuals with episodic cluster headache during their active phase and individuals with chronic cluster headache. In this study, we investigated whether infusions of PACAP and VIP caused alterations in plasma levels of VIP and their potential contribution to induced cluster headache attacks. Participants received either PACAP or VIP infusion for 20 min on 2 separate days with an interval of at least 7 days in between. Blood collection was performed at T0, T20, T30, and T90. Plasma levels of VIP were measured using a validated radioimmunoassay method. Blood samples were collected from participants with episodic cluster headache in the active phase (eCHA, n = 14), remission (eCHR, n = 15), and from participants with chronic cluster headache (cCH, n = 15). Baseline levels of VIP did not differ among the three groups (p = 0.1161). During PACAP infusion, mixed-effects analysis revealed a significant increase in plasma levels of VIP in eCHA (p = 0.0300) and eCHR (p = 0.0058) but not in cCH (p = 0.2930). We found no difference in the increase of plasma VIP levels between patients who developed PACAP38- or VIP-induced attacks. Cluster headache attacks induced by PACAP38 or VIP infusion are not associated with changes in plasma levels of VIP. Further studies are needed to investigate the role of VIP and the parasympathetic system in cluster headache. The parent study is registered at ClinicalTrials.gov (NCT03814226).

Vasoactive intestinal peptide secreting tumour: An overview.

Vasoactive intestinal peptide (VIP) secreting tumour (VIPoma) is a rare functional neuroendocrine tumour that typically arises from pancreatic islet cells. These present as sporadic, solitary pancreatic neoplasias with an estimated incidence of one in ten million individuals per year. Only around 5% of VIPomas are associated with multiple endocrine neoplasia type I syndrome. Excessive VIP secretion produces a clinical syndrome characterized by refractory watery diarrhoea, hypokalemia and metabolic acidosis. These coupled with elevated plasma levels of VIP are diagnostic. The majority of VIPomas are malignant and have already metastasized at the time of diagnosis (60%). Metastases occur most frequently in the liver, or regional lymph nodes, lungs, kidneys and bones. Some reports of skin metastases have been documented. Complete surgical resection continues to be the only potentially curative treatment. However, when the neoplasia cannot be excised completely, surgical debulking may provide palliative benefit. Other palliative options have included recently the peptide receptor radionuclide therapy which has shown to be effective and well-tolerated. This article will review all aspects of pancreatic VIPomas highlighting aspects such as clinical presentation, diagnosis and management.

VIP plasma levels associate with survival in severe COVID-19 patients, correlating with protective effects in SARS-CoV-2-infected cells.

Infection by SARS‐CoV‐2 may elicit uncontrolled and damaging inflammatory responses. Thus, it is critical to identify compounds able to inhibit virus replication and thwart the inflammatory reaction. Here, we show that the plasma levels of the immunoregulatory neuropeptide VIP are elevated in patients with severe COVID‐19, correlating with reduced inflammatory mediators and with survival on those patients. In vitro, vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase‐activating polypeptide (PACAP), highly similar neuropeptides, decreased the SARS‐CoV‐2 RNA content in human monocytes and viral production in lung epithelial cells, also reducing cell death. Both neuropeptides inhibited the production of proinflammatory mediators in lung epithelial cells and in monocytes. VIP and PACAP prevented in monocytes the SARS‐CoV‐2‐induced activation of NF‐kB and SREBP1 and SREBP2, transcriptions factors involved in proinflammatory reactions and lipid metabolism, respectively. They also promoted CREB activation, a transcription factor with antiapoptotic activity and negative regulator of NF‐kB. Specific inhibition of NF‐kB and SREBP1/2 reproduced the anti‐inflammatory, antiviral, and cell death protection effects of VIP and PACAP. Our results support further clinical investigations of these neuropeptides against COVID‐19.

Chronic Diarrhea and Weight Loss in an 18-month-old Boy.

Chronic Diarrhea and Weight Loss in an 18-month-old Boy.

Changes in plasma levels of cholecystokinin, neurotensin, VIP and PYY in gastric and colorectal cancer – Preliminary results

Physiological roles of enterohormones such as secretion, absorption and digestion were supported by clinical data. Overexpression of cholecystokinin (CCK), neurotensin (NT) and vasoactive intestinal peptide (VIP) receptors occur in gastrointestinal (GI) malignancies. The aim of the paper was to compare plasma levels of CCK, peptide YY (PYY), VIP and NT in patients with gastrointestinal malignancies and healthy controls. The study included 80 patients (37 men and 43 women) with GI malignancies (20 with gastric and 60 with colorectal cancers). Median age of the patients was 62.9 years (range: 40–85 years). Control group was comprised of 30 healthy persons with median age 59.8 years (range: 40–82 years). Fasting plasma concentrations of CKK, PYY, NT, and VIP were determined at rest, using ELISA kits for automated systems. Comparative analysis of enterohormone levels in patients with various types of gastrointestinal malignancies demonstrated presence of some cancer-specific alterations. Patients with gastric cancers presented with lower plasma concentrations of CCK than healthy controls and individuals from colorectal cancers (p = 0.02). The highest plasma concentrations of neurotensin was found in colorectal cancer patients in comparison to gastric (p = 0.02). The plasma levels of VIP observed in gastric cancer group were lower than in colorectal cancer patients (p = 0.01). Patients with GI malignancies may present with tumor-specific alterations in plasma enterohormone levels.

Association between neuroendocrine tumors biomarkers and primary tumor site and disease type based on total 68Ga-DOTATATE-Avid tumor volume measurements.

To determine the association between neuroendocrine tumor (NET) biomarker levels and the extent of disease as assessed by 68Ga DOTATATE PET/CT imaging. A retrospective analysis of a prospective database of patients with NETs. Fasting plasma chromogranin A (CgA), neuron-specific enolase (NSE), gastrin, glucagon, vasoactive intestinal peptide (VIP) and pancreatic polypeptide (PP), and 24-h urinary 5-hydroxyindoleacetic acid (5-HIAA) levels were measured. Correlation between biomarkers and total 68Ga-DOTATATE-avid tumor volume (TV) was analyzed. The analysis included 232 patients. In patients with pancreatic NETs (n = 112), 68Ga-DOTATATE TV correlated with CgA (r = 0.6, P = 0.001, Spearman). In patients with multiple endocrine neoplasia type 1 (n = 39), 68Ga-DOTATATE TV correlated with glucagon (r = 0.5, P = 0.01) and PP levels (r = 0.5, P = 0.049). In patients with von Hippel-Lindau (n = 24), plasma VIP (r = 0.5, P = 0.02) and PP levels (r = 0.7, P < 0.001) correlated with 68Ga-DOTATATE TV. In patients with small intestine NET (SINET, n = 74), 68Ga-DOTATATE TV correlated with CgA (r = 0.5, P = 0.02) and 5-HIAA levels (r = 0.7, P < 0.001), with 5-HIAA ≥8.1 mg/24 h associated with metastatic disease with high positive (81.8%) and negative (85.7%) predictive values (P = 0.001). 68Ga-DOTATATE TV in patients with NET of unknown primary (n = 16) and those with NET of other primary location (n = 30) correlated with 5-HIAA levels (r = 0.8, P = 0.002 and r = 0.7, P = 0.02 respectively). Our data supports the use of specific NET biomarkers based on the site of the primary NET and the presence of hereditary syndrome-associated NET. High urinary 5-HIAA levels indicate the presence of metastatic disease in patients with SINET.

Granulocyte colony-stimulating factor provides protection against cardiovascular autonomic neuropathy in streptozotocin-induced diabetes in rats

AimsCardiovascular autonomic neuropathy (CAN) is a relatively common and detrimental complication of diabetes mellitus (DM). Dysregulation of neuropeptides, such as calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP), are thought to play significant roles in diabetes-related cardiovascular disease. Accumulating evidence indicates the neuroprotective effects of granulocyte-colony stimulating factor (G-CSF) in different neurological disorders. The purpose of the study is to investigate the role of CGRP and VIP and possible effects of G-CSF on CAN in type I DM model in rats. MethodsDiabetes was induced by intraperitoneal injection of streptozotocin (STZ) for 14 rats. Seven rats served as controls and 6 rats were administered G-CSF alone. DM group was randomly divided into 2 groups and received either 1mL/kg saline (DM+saline group) or 100μg/kg/day G-CSF (DM+G-CSF group) for 4 weeks. Following electrocardiography (ECG), GCRP and VIP levels were measured in plasma samples. ResultsDiabetes promoted a significant prolongation in the corrected QT interval (cQT) (P<0.001) whereas G-CSF administration significantly shortened cQT interval (P<0.05). Plasma VIP and CGRP levels of saline treated DM group were significantly lower than those of control group (P<0.05). G-CSF treatment significantly prevented the reduction in plasma VIP and CGRP levels (P<0.01 and P<0.05, respectively). Also, correlation analysis showed a significant negative correlation between the cQT and neuropeptide levels. ConclusionsThis study suggests that G-CSF can be effective in CAN by means of neuroprotection, and plasma VIP and CGRP levels can be used for the assessment of autonomic and sensory functions in diabetes.

A Study of the acupuncture point embedding therapy on slow transit constipation along with colon transmission function,plasma SP and VIP

Objective To explore the clinical efficacy of acupuncture point embedding therapy in the treatment of slow transit constipation （STC）and the influence on the colon transmission function,plasma substance P（SP）, vasoactive intestinal peptide（VIP）. Methods A total of 128 slow transit constipation patients were involved in the study and divided randomly into two groups by using stochastic indicator： a treatment group （treated with acupuncture point embedding therapy） and a control group （treated with lactulose oral liquid）. The clinical effects, colon transmission function, the influence of SP, and VIP were observed for STC patients. Results In the treatment group, CCS score was （13.52±3.93） before treatment and（8.15±3.77） after the treatment. In the control group CCS score was （14.11±4.24） and （9.01±2.93） respectively before and after the treatment, CCS score in both groups showed significantly improvement after the treatment （P〈0.01）, and there was no significant difference between groups （P〉0.05）. The plasma SP and VIP level of the two groups after the treatment [treatment group （46.73±1.50） ng/L,（206.10±12.14） ng/L, the control group（40.92±6.25）ng/L,（214.73± 7.62）ng/L] were also improved than before [treatment group was（26.66±0.88）ng/L, （332.68±17.84）ng/L, the control group was （23.32±1.75）ng/L,（306.22±20.01）ng/L], with statistically significant（P〈0.05）, and the difference between the two groups were also significant（P〈0.05）.Conclusion The acupuncture point embedding therapy is effective for STC, and it can regulate the level of SP and VIP. Key words: Acupuncture point embedding therapy; Slow transit constipation; Colon transmission function; SP; VIP

Low levels of vasoactive intestinal peptide are associated with Chagas disease cardiomyopathy

The interconnection between immune and neuroendocrine systems influences regulation of inflammatory responses. The possible relevance that this integrative response may have during the course of Chagas disease remains poorly characterized. In this context, our study was designed to determine the expression of vasoactive intestinal peptide (VIP), a neuropeptide with anti-inflammatory properties, in blood from the indeterminate and cardiac polarized forms of Chagas disease. Moreover, we determined whether the differential expression of VIP is associated with the development of cardiomyopathy in individuals infected with Trypanosoma cruzi. Finally, we analyzed gene polymorphisms of VIP receptors, VPAC1 and VPAC2, and performed correlation analysis of these polymorphisms with the different clinical forms of Chagas disease. Our results demonstrated that low plasma levels of VIP were associated with the cardiac morbidity in Chagas disease. Accordingly, correlation analysis showed that low plasma levels of VIP were associated with worse cardiac function, as determined by left ventricular ejection fraction and left ventricular diastolic diameter values. Polymorphism analysis showed a significant association between VPAC1 and the indeterminate form of Chagas disease development. Our data indicate that VIP expression and its receptors' polymorphism may be important in determining susceptibility to progression from mild to severe forms of Chagas disease.

Correlation between diarrhea type irritable bowel syndrome overlapped with functional dyspepsia andpsychology and gastrointestinal hormones

Objective To investigate the psychological status of diarrhea type irritable bowel syndrome （D-IBS） patients overlapped with functional dyspepsia （FD） and its relationship with the changes of brain-gut peptides and cytokines levels. Methods A total of 190 D-IBS-FD overlapped patients and 30 healthy controls were selected and all of them completed the questionnaire. The adult psychological testing system was applied for the Symptom Checklist （SCL-90） assessment. Plasma levels of 5-hydroxytryptamine （5-HT）, somatostatin （SS）, vasoactive intestinal peptide （VIP）, endothelin （ET）, interleukin （IL）-10 and IL-12 were measured in 59 randomly selected patients.Single factor analysis of variance and LSD test were performed for statistical analysis. Results In D- IBS-FD overlapped patients, the plasma 5-HT levels of the D-IBS patients and the FD patients were （1906.83±676. 88） μg/L and （1745. 53±653. 23） μg/L respectively, both of them were significant higher than those of control group [（1289.44±918.45） μg/L, LSD test, both P〈0. 051. However the levels of VIP and IL-10 were significant lower than those of control group （LSD test, both P〈0.01）. In D-IBS patients, the plasma level of SS was significantly lower than that of control group （LSD test, P=0. 025） ; the level of ET was significantly higher than that of control group and FD patients （LSD test, both P〈0. 05）. In D-IBS-FD overlapped patients, the scores of anxiety, depression and opponent were higher than those of control group （F=5. 114, 4. 555 and 10. 285, all P〈0.05）. The plasma VIP and SS levels of patients with anxiety or depression were lower than those of control group （LSD test, both P〈0.05）. The plasma VIP level was lower than that of patients without psychological disorders （LSD test, P=0. 005）. The plasma ET level of patients with disease course over five years was significantly higher than that of patients with disease course less than one year or between one and five years （LSD test, both P〈0.05）, and the IL-10 level was significantly lower than that of patients with disease course less than one year （LSD test, P=0. 004）. Conclusions There were sub-healthy psychology state in D-IBS-FD overlapped patients. The overlapping symptoms may be correlated with disease course, psychological disorder, the increased plasma 5-HT level and the decreased IL-10 level. There was close correlation between the lower gastrointestinal symptoms and the decreased levels of VIP, SS and the increased level of ET. Key words: Irritable bowel syndrome; Dyspepsia; Anxiety; Serotonin; InterIeukin 10; Vasoactive intestinal peptide; Somatostatin; Endotoxins

Neurogenic markers of the inflammatory process in atopic dermatitis: relation to the severity and pruritus

IntroductionAtopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease, characterized by eczematous skin lesions and intensive pruritus. Recent studies have shed light on the role of the nervous system in the pathogenesis of AD. It can influence the course of the disease through an altered pattern of cutaneous innervation and abnormal expression of neuropeptides in the lesional skin.AimThe aim of the study was to evaluate plasma concentrations of the nerve growth factor (NGF), substance P (SP) and vasoactive intestinal peptide (VIP) in AD patients in comparison to two control groups (healthy volunteers and patients suffering from psoriasis). Correlations between plasma levels of evaluated parameters, severity of the disease and selected clinical parameters (skin prick tests, total and antigen specific IgE levels) were also analysed.Material and methodsSeventy-five patients with AD, 40 patients with psoriasis and 40 healthy volunteers were included into the study. Patients with AD included 52 persons suffering from an extrinsic and 23 from an intrinsic type of the disease. The severity of skin lesions was assessed with SCORAD index. Pruritus was evaluated on the basis of the questionnaire assessing the extent, frequency and intensity of pruritus. Commercial enzyme-linked immunosorbent assays (SP, NGF: R&D Systems; and VIP: Phoenix Pharmaceuticals) were used to assess the neuropeptide and NGF plasma levels.ResultsNerve growth factor and VIP plasma concentrations were significantly higher in AD patients compared to psoriatic patients and healthy subjects. Substance P plasma concentrations were elevated in the extrinsic type of AD and psoriasis comparing to healthy volunteers. There were no statistically significant differences in NGF, SP and VIP plasma concentrations between the extrinsic and intrinsic type of AD. There was also no correlation between plasma levels of evaluated parameters (NGF, SP, VIP) and SCORAD index in both types of AD. However, plasma SP concentration correlated with intensity of pruritus in AD patients. Plasma VIP concentrations correlated with intensity of pruritus in the intrinsic type of AD and with IgE-mediated sensitization to moulds in the extrinsic type of disease.ConclusionsOur findings confirm that NGF and VIP play a prominent role in atopic inflammatory reactions and may serve as good alternative biomarkers of AD. The results of this study also suggest a similar important role of neuroimmune interactions in both variants of AD. Increased SP plasma concentrations in both AD and psoriasis point to its possible role in modulating immune-mediated inflammation in different chronic inflammatory skin diseases. Moreover, SP and VIP seem to influence the course of AD by increasing pruritus, whereas an elevated plasma VIP level in AD patients may be related to a risk of developing IgE-mediated sensitization to certain airborne allergens.

Impacting patient-centred outcomes in COPD: exacerbations and hospitalisations

Graded doses of 0.6, 1.3, and 3.3 pmol/kg/min of vasoactive intestinal peptide (VIP) were intravenously infused over 30 minute periods in four healthy volunteers and plasma VIP levels were measured by radioimmunoassay. Even with the smallest dose of VIP, plasma concentrations rose markedly above normal values. Infusion of higher VIP doses resulted in mean plateau levels of circulating VIP which were in the range of VIP values found in the Verner-Morrison syndrome. After cessation of the VIP infusions, plasma VIP levels fell strikingly by first order kinetics with an average disappearance half-time of one minute. The apparent metabolic clearance rate was about 9 ml/kg/min and the apparent volume of distribution for VIP was approximately 14 ml/kg. During infusion of the highest VIP dose, previously shown to induce one-fifth maximum pancreatic juice secretion, plasma concentrations of glucose, free fatty acids, and calcium were slightly but significantly raised, the pulse rate and the amplitude of blood pressure were increased, and cutaneous flushing occurred. The spectrum of effects accords well with some abnormalities seen in the Verner-Morrison syndrome. The present data, however, do not support a role for VIP as a circulating hormone, at least under physiological conditions.

Vasoactive intestinal peptide impairs leucocyte migration but fails to modify experimental murine colitis

Inflammatory bowel diseases are chronic inflammatory disorders of the gastrointestinal tract. Vasoactive intestinal peptide (VIP) is a neuropeptide with known anti-inflammatory activity. We have demonstrated previously that administration of VIP inhibits leucocyte migration in a murine model of delayed-type hypersensitivity, and anti-inflammatory efficacy is supported by other studies. The aim of this study was to investigate the VIP effects in a murine model of intestinal inflammation. Colitis was induced in BALB/c mice by a 2.5 mg enema of 2,4,6-trinitrobenzenesulphonic acid (TNBS) and the mice were killed on day 7. Mice were administered either a 3-day (therapeutic) or 7-day (prophylactic) constant infusion of VIP by subcutaneously implanted mini-osmotic pumps, or intraperitoneal (i.p.) injection of VIP on alternate days over 7 days. Clinical disease scores, weight changes, histopathology of colon tissues, plasma VIP levels, cytokine levels and chemotaxis of peripheral blood mononuclear cells were evaluated. After administration of TNBS, mice quickly developed severe colitis accompanied by dramatic body weight loss (20% by day 6) and high mortality (30%). Prophylactic treatment using high-dose VIP abrogated leucocyte chemotaxis; however, it failed to ameliorate the weight loss and mortality. Moreover, VIP delivered either by constant infusion or i.p. failed to modify the clinical, histological or cytokine markers of disease. Our studies show that, despite an ability to inhibit chemokine-induced chemotaxis of mononuclear cells, VIP was unable to modulate TNBS-induced colitis. This contrasts with the efficacy of VIP in models of mild inflammatory disease and suggests that VIP is unlikely to provide a useful model for novel anti-IBD therapy.

Levels of vasoactive intestinal peptide, cholecystokinin and calcitonin gene-related peptide in plasma and jejunum of rats following traumatic brain injury and underlying significance in gastrointestinal dysfunction.

To study the alterations of brain-gut peptides following traumatic brain injury (TBI) and to explore the underlying significance of these peptides in the complicated gastrointestinal dysfunction. Rat models of focal traumatic brain injury were established by impact insult method, and divided into 6 groups (6 rats each group) including control group with sham operation and TBI groups at postinjury 3, 12, 24, 72 h, and d 7. Blood and proximal jejunum samples were taken at time point of each group and gross observations of gastrointestinal pathology were recorded simultaneously. The levels of vasoactive intestinal peptide (VIP) in plasma, calcitonin gene-related peptide (CGRP) and cholecystokinin (CCK) in both plasma and jejunum were measured by enzyme immunoassay (EIA). Radioimmunoassay (RIA) was used to determine the levels of VIP in jejunum. Gastric distension, delayed gastric emptying and intestinal dilatation with a large amount of yellowish effusion and thin edematous wall were found in TBI rats through 12 h and 72 h, which peaked at postinjury 72 h. As compared with that of control group (247.8+/-29.5 ng/L), plasma VIP levels were significantly decreased at postinjury 3, 12 and 24 h (106.7+/-34.1 ng/L, 148.7+/-22.8 ng/L, 132.8+/-21.6 ng/L, respectively), but significantly increased at 72 h (405.0+/-29.8 ng/L) and markedly declined on d 7 (130.7+/-19.3 ng/L). However, Plasma levels CCK and CGRP were significantly increased through 3 h and 7 d following TBI (126-691% increases), with the peak at 72 h. Compared with control (VIP, 13.6+/-1.4 ng /g; CGRP, 70.6+/-17.7 ng/g); VIP and CGRP levels in jejunum were significantly increased at 3 h after TBI (VIP, 35.4+/-5.0 ng/g; CGRP, 103.8+/-22.1 ng/g), and declined gradually at 12 h and 24 h (VIP, 16.5+/-1.8 ng/g, 5.5+/-1.4 ng/g; CGRP, 34.9+/-9.7 ng/g, 18.5+/-7.7 ng/g), but were significantly increased again at 72 h (VIP, 48.7+/-9.5 ng/g; CGRP, 142.1+/-24.3 ng/g), then declined in various degrees on d 7 (VIP, 3.8+/-1.1 ng/g; CGRP, 102.5+/-18.1 ng/g). The CCK levels in jejunum were found to change in a similar trend as that in plasma with the concentrations of CCK significantly increased following TBI (99-517% increases) and peaked at 72 h. Traumatic brain injury can lead to significant changes of brain-gut peptides in both plasma and small intestine, which may be involved in the pathogenesis of complicated gastrointestinal dysfunction.

Gastric emptying and plasma levels of gastrointestinal hormones in patients with peptic ulcer.

To study the plasma level of gastrointestinal hormones and the time of gastric emptying in patients with peptic ulcer. Thirty patients with gastric ulcer (GU), 29 patients with duodenal ulcer (DU), and 12 healthy controls were studied. Plasma levels of somatostatin (SS), vasoactive intestinal peptide (VIP) and substance P (SP) were measured by radioimmunoassay. Gastric emptying half-time (GET1/2) was measured by the TC-99(m) resin/solid meal method. GET1/2 was significantly longer in the GU patients than that in the healthy controls (65.9 ± 14.8 min vs 53.3 ± 4.3 min, P < 0.01) and plasma VIP levels were significantly higher (37.5 ± 10.7 ng/L vs 18.4 ± 5.9 ng/L, P < 0.05).There was a significant positive correlation between GET1/2 and plasma VIP levels (r = 0.55, P < 0.01). No significant differences were found in SS and SP levels when GU patients were compared with healthy controls (P > 0.05). GET1/2 was markedly shorter in the DU patients than in the healthy controls (41.7 ± 10.2 min vs 53.3 ± 4.3 min, P < 0.01) and plasma SS levels were significantly lower (6.4 ± 2.5 ng/L vs 11.9 ± 3.4 ng/L, P < 0.01). There was a significant positive correlation between GET1/2 and SS levels (r = 0.56, P < 0.01). Plasma SP levels in the DU patients were significantly higher than those in the healthy controls (54.4 ± 12.7 ng/L vs 41.6 ± 5.8 ng/L, P < 0.01). There was a significant negative correlation between GET1/2 and SP levels (r = -0.68, P < 0.01). No significant differences were found in the plasma VIP levels when DU patient were compared to healthy controls (P > 0.05). Elevation in VIP may contribute to occurrence of GU and its associated delay in GET1/2. Increased SP and reduced SS may play important roles in GET1/2 acceleration and in the pathogensis of DU.

Elevated levels of plasma vasoactive intestinal peptide in human acute myocardial infarction

The plasma levels of vasoactive intestinal peptide in peripheral vein were measured in human acute myocardial infarction. The plasma vasoactive intestinal peptide level was increased within 1 h after the onset of the symptoms of acute myocardial infarction (Group 1, n = 9), compared with normal values (6.3 ± 0.7 vs. 2.8 ± 0.9 pg/ml, P < 0.05). Two or more hours after the onset of acute myocardial infarction there was no subsequent increase in peripheral plasma vasoactive intestinal peptide levels ( n = 26). Ten days after the onset of acute myocardial infarction, the elevated plasma vasoactive intestinal peptide levels in Group 1 had normalized (3.5 ± 0.5 pg/ml).

The Effect of Dietary Sodium on the Concentrations of Vasoactive Intestinal Peptide in Plasma and Lung

In this study, we sought to determine whether changes in the concentration of vasoactive intestinal peptide (VIP) in the lung might explain the increase in bronchial reactivity associated with high sodium diets. Male Sprague-Dawley rats, eight in each group, were placed on low-sodium, normal-sodium, or high-sodium diets and distilled drinking water ad libitum for 7 days. On the day of study, blood was sampled to determine plasma VIP concentration and the lungs were harvested and snap frozen in liquid nitrogen. VIP was measured in plasma and tissue extracts by radioimmunoassay. The VIP concentrations in both lung and plasma varied with dietary sodium. Plasma VIP level was significantly higher in the rats that had received the low-sodium diet (51.45 +/- 7.35 pmol L-1) than in the rats that had received the high-sodium diet (29.84 +/- 6.83; p < 0.05). In the lung, VIP level was greater in the rats that had received the normal-sodium diet (378.13 +/- 41.68 fmol/g) than in rats that had received either the low-sodium diet (137.30 +/- 26.11 fmol/g; p < 0.0005) or the high-sodium diet (182.64 +/- 28.63 fmol/g; p < 0.005). The lower plasma and pulmonary concentrations of VIP observed in rats that had received a high-sodium diet suggest that VIP may play a role in the increased bronchial reactivity reported with this diet.

Low plasma concentrations of VIP and elevated levels of other neuropeptides during exacerbations of asthma

Neuropeptides in the lung occur in neurons, neuroendocrine and inflammatory cells. Their widespread distribution and physiological effects suggest that they may play important roles in asthma. We investigated whether, during an exacerbation of asthma, patients displayed changes in plasma levels of the neuropeptides vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP), substance P (SP), and neuropeptide Y (NPY). Venous blood from 25 adult patients attending the emergency ward with an exacerbation of asthma was sampled before and after treatment. Plasma levels of VIP-, SP-, CGRP- and NPY-like immunoreactivity (-LI) were determined by immunoassay, and the results obtained were compared with findings in 21 healthy controls. The mean plasma levels of VIP-LI were lower in patients (3.4 +/- 0.4 pmol.l-1) than in controls (10.4 +/- 0.7 pmol.l-1), whereas the levels of CGRP-LI (43.7 +/- 3.4 pmol.l-1), SP-LI (4.6 +/- 0.4 pmol.l-1) and NPY-LI levels (159 +/- 6 pmol.l-1) were higher in patients than in controls (21.1 +/- 3.4; 2.2 +/- 0.2 and 105 +/- 8 pmol.l-1, respectively). A relationship was seen between the reversibility of obstruction, expressed as improvement of peak expiratory flow upon treatment, and the neuropeptide levels, such that lower VIP-LI levels and higher CGRP-LI levels correlated with less reversibility. Plasma levels of neuropeptides, VIP-LI and CGRP-LI in particular, may therefore be employed as predictors of responsiveness to bronchodilatory therapy.

The effects of a high sodium diet on the metabolism and secretion of vasoactive intestinal peptide in the rabbit.

1. In view of previous observations that the metabolism of vasoactive intestinal peptide (VIP) is significantly increased in sodium-depleted rabbits, we wished to determine whether a high sodium intake also leads to alterations in VIP metabolism. We performed metabolic clearance studies in rabbits maintained on a high sodium diet and normal control diets. These studies were performed both before and after the administration of 1.5 mmol kg-1 of sodium intravenously to observe the effects of an acute increase in body sodium. 2. The rabbits maintained on the high sodium diet had a significantly lower basal plasma VIP level (P less than 0.025), a lower metabolic clearance rate (MCR) of the peptide (P less than 0.025) and a lower secretion rate (P less than 0.005), compared with the normal control animals. These differences were maintained following the intravenous sodium infusion. 3. The administration of the intravenous sodium infusion resulted in a further decrease in MCR in the rabbits on the high sodium diet (P less than 0.05). 4. These results confirm that VIP metabolism is affected by high dietary intake of sodium, as well as a low sodium intake, adding further support to the hypothesis that VIP may be involved in sodium homeostasis.

Cerulein-induced acute pancreatitis in the rat. Study of pancreatic secretion and plasma VIP and secretin levels.

A study was made with different doses of cerulein (2, 4, 10 and 20 micrograms/kg) administered subcutaneously to rats by four injections at intervals of 1 hr; the aim of this work was to study exocrine pancreatic secretion of the rat under cerulein-induced acute pancreatitis, analyzing enzyme and hydroelectrolyte secretion of pancreatic juice. A further aim was to study the relationship between the dose of cerulein and the plasma levels of peptides controlling hydroelectrolyte secretion of the pancreas, like secretin and vasoactive intestinal peptide (VIP). At the lowest dose schedule, the amounts of total protein and enzymes (amylase and trypsin) in pancreatic juice decreased significantly, plasma amylase increased, and the pancreas became edematous. Higher doses magnified these effects. By contrast, ductular function (flow and HCO3-) was well preserved in cerulein-treated rats, and this was probably due to the significant increase in plasma levels of immunoreactive secretin whereas VIP levels were unchanged. The secretin released by treatment with cerulein is able to palliate the lack of flow from acinar origin that is affected in the process of acute pancreatitis, being a beneficial response to the cerulein treatment.