Plasma Vasoactive Intestinal Polypeptide Levels Research Articles

Methamphetamine-Induced Vaginal Lubrication & Associated Hormonal Changes

ABSTRACT Introduction Vaginal dryness is an issue that affects millions of women, creating a situation that often leads to painful sexual experiences and diminished pleasure and self-esteem. Though the physiology of vaginal lubrication in response to sexually arousing stimuli is established, no treatment, other than topical lubricants, is available for women suffering from vaginal dryness. Previous research from our lab reported that female methamphetamine (meth) users experience immediate and noticeable vaginal lubrication when they inject the drug intravenously (IV). A warming or flushing sensation spreading from the chest area down into the pelvic region accompanied this lubrication. Understanding the mechanisms mediating this previously undescribed phenomenon may reveal a potential target for future pharmaceutical development to enhance a woman's natural levels of vaginal lubrication. We have reported that injections of meth also increase vaginal lubrication in rats in a dose-dependent manner. Plasma levels of several signaling molecules known to influence vaginal lubrication, including the steroid hormones estradiol, progesterone, and testosterone, as well as the gaseous vasodilator nitric oxide, increase at specific time points following IV meth in female rats. Accordingly, we were able to decrease the amount of vaginal fluid produced by pre-treating the animals with the nitric oxide synthase inhibitor, L-NAME, prior to meth. Objective The present work expands the aforementioned findings by measuring plasma levels of vasoactive intestinal polypeptide (VIP), an established mediator of female sexual arousal, and corticosterone, a steroid hormone implicated in drug addiction, after IV injections of meth. We also determined the involvement of estradiol in meth-induced vaginal lubrication using an estrogen receptor antagonist. Methods We implanted adult female Wistar rats with chronic indwelling jugular catheters and allowed them at least one week to recover from surgery. We pre-treated the rats with fulvestrant, an estrogen receptor antagonist, and then anesthetized them with isoflurane gas before injecting them intravenously with meth via the implanted catheter. A pre-weighed cotton-tipped swab, inserted into the vaginal canal, collected fluid secreted following the administration of meth. The change in the weight of the swab before and after meth indicated the amount of fluid produced. In a separate group of rats, we used the jugular catheter to remove blood at various time points (1-60 min) following the meth injections to measure plasma levels of VIP and corticosterone. Results Although we have not yet completed these experiments, we hypothesize that the inhibition of estrogen receptors will reduce meth-induced vaginal lubrication similar to the reduction produced by L-NAME. Further, we predict that both VIP and corticosterone levels will increase between 5 and 20 min after the injections of meth, similarly to the other signaling molecules we measured previously. Conclusions These findings have far-reaching and potentially life-changing implications, as the majority of women will experience vaginal dryness a least once in their lifetimes, if not chronically. The underlying mechanisms of meth-induced vaginal lubrication may provide the necessary pharmacological target to treat vaginal dryness. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Goeders is on the Scientific Advisory Boards for Embera NeuroTherapeutics and JanOne; however, the work of these companies is unrelated to the submitted abstract.

Plasma Levels of CGRP During a 2-h Infusion of VIP in Healthy Volunteers and Patients With Migraine: An Exploratory Study

IntroductionThe activation of perivascular fibers and the consequent release of vasoactive peptides, including the vasoactive intestinal polypeptide (VIP), play a role in migraine pathogenesis. A 2-h infusion of VIP provoked migraine, but the mechanisms remain unknown. We investigated whether 2-h infusion of VIP caused alterations in plasma levels of the calcitonin gene-related peptide (CGRP) and whether any changes might be related to the induced migraine attacks.Materials and MethodsWe enrolled individuals with episodic migraine without aura and healthy participants to randomly receive a 2-h infusion of either VIP (8 pmol/kg/min) or placebo (sterile saline) in two randomized, placebo-controlled crossover trials. We collected clinical data and measured plasma levels of VIP and CGRP at fixed time points: at baseline (T0) and every 30 min until 180 min (T180) after the start of the infusion.ResultsBlood samples were collected from patients with migraine (n = 19) and healthy individuals (n = 12). During VIP infusion, mixed effects analysis revealed a significant increase in plasma CGRP (p = 0.027) at T30 (vs. T180, adjusted p-value = 0.039) and T60 (vs. T180, adjusted p-value = 0.027) in patients with migraine. We found no increase in plasma CGRP during VIP-induced migraine attacks (p = 0.219). In healthy individuals, there was no increase in plasma CGRP during VIP (p = 0.205) or placebo (p = 0.428) days.DiscussionPlasma CGRP was elevated in patients with migraine during a prolonged infusion of VIP, but these alterations were not associated with VIP-induced migraine attacks. Given the exploratory design of our study, further investigations are needed to clarify the role of CGRP in VIP-induced migraine.Clinical Trial RegistrationClinicalTrials.gov, identifier: NCT03989817 and NCT04260035.

Vasoactive intestinal polypeptide plasma levels associated with affective symptoms and brain structure and function in healthy females

Vasoactive intestinal polypeptide (VIP) is a neuroendocrine peptide distributed throughout the human body, including the CNS, where it is particularly abundant in brain regions associated with anxiety and depression. Based on earlier studies indicating that peripheral VIP may cross through the blood–brain barrier, we hypothesized plasma VIP levels to be associated with symptoms of anxiety and depression, as well as brain volume and resting-state functional connectivity in the amygdala, hippocampus, parahippocampus, and orbitofrontal cortex. Plasma VIP concentrations and anxiety/depression symptoms were measured in 37 healthy females. Functional and structural magnetic resonance imaging were used to evaluate functional connectivity and brain volume respectively, and their associations with VIP concentrations within brain regions associated with anxiety and depression. Negative correlations were found between VIP levels and symptoms of anxiety (r = − 0.44, p = 0.002) and depression (r = − 0.50, p = 0.001). Functional connectivity demonstrated significant VIP-dependent positive associations between the amygdala seed region with both the right parahippocampus (t(33) = 3.1, pFDR = 0.02) and right lateral orbitofrontal cortex (OFC; t(33) = 2.9, pFDR = 0.02). Moreover, VIP concentrations were significantly, positively correlated with brain volume in the left amygdala (r = 0.28, p = 0.007) and left lateral OFC (r = 0.29, p = 0.004). The present findings highlight a potential role for VIP in the neurobiology of affective symptoms.

Part II: Biochemical changes after pituitary adenylate cyclase-activating polypeptide-38 infusion in migraine patients

Background Intravenous infusion of pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) provokes migraine attacks in 65-70% of migraine without aura (MO) patients. We investigated whether PACAP38 infusion causes changes in the endogenous production of PACAP38, vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), tumour necrosis factor alpha (TNFα), S100 calcium binding protein B (S100B), neuron-specific enolase and pituitary hormones in migraine patients. Methods We allocated 32 previously genotyped MO patients to receive intravenous infusion PACAP38 (10 pmol/kg/minute) for 20 minutes and recorded migraine-like attacks. Sixteen of the patients were carriers of the risk allele rs2274316 ( MEF2D), which confers increased risk of MO and may regulate PACAP38 expression, and 16 were non-carriers. We collected blood samples at baseline and 20, 30, 40, 60 and 90 minutes after the start of the infusion. A control group of six healthy volunteers received intravenous saline. Results PACAP38 infusion caused significant changes in plasma concentrations of VIP ( p = 0.026), prolactin ( p = 0.011), S100B ( p < 0.001) and thyroid-stimulating hormone (TSH; p = 0.015), but not CGRP ( p = 0.642) and TNFα ( p = 0.535). We found no difference in measured biochemical variables after PACAP38 infusion in patients who later developed migraine-like attacks compared to those who did not ( p > 0.05). There was no difference in the changes of biochemical variables between patients with and without the MEF2D-associated gene variant ( p > 0.05). Conclusion PACAP38 infusion elevated the plasma levels of VIP, prolactin, S100B and TSH, but not CGRP and TNFα. Development of delayed migraine-like attacks or the presence of the MEF2D gene variant was not associated with pre-ictal changes in plasma levels of neuropeptides, TNFα and pituitary hormones.

The vasoactive intestinal polypeptide (VIP) levels at the patients with ankylosing spondylitis and its association with inflammation markers

Vasoactive intestinal polypeptide (VIP) is a neuropeptide from secretin/glukagon family. Recently, the importance of VIP is becoming more evident, and it is thought that VIP is playing an important regulatory role between neuroendocrine-immune-gastrointestinal systems. In this study, we have tried to evaluate the potential role of VIP in patients with ankylosing spondylitis (AS). In this study, 40 patients (30 male and 10 female) with AS and 40 healthy controls were included. X-ray examinations and scoring of sacroiliac joints of the patients with AS were done according to 1984 Modified New York Criteria for AS. All patients have been assessed with Bath Ankylosing Spondylitis Disease Activity Index. Platelet counts were significantly higher in study group (P < 0.05) in contrast to levels of the hemoglobin. The mean VIP levels were 4.2 ± 1.8 (pg/mL) for study group and 2.8 ± 0.8 (pg/mL) for controls. These results were statistically significant (P < 0.05). There was not any correlation between plasma VIP levels with CRP, ESR, Hb, BASDAI results and radiological scoring of the patients (P > 0.05) in contrast to our expectations. However, platelet counts and VIP levels were correlated significantly (P = 0.03). Our data demonstrate that VIP tended to be high in patients with AS when compared with healthy subjects and correlated with platelet counts significantly, for the first time at the literature. According to this study, VIP may have potential role in the pathogenesis of AS, and it is a potential candidate for many kinds of therapies.

Effect of fluoxetine on depression-induced changes in the expression of vasoactive intestinal polypeptide and corticotrophin releasing factor in rat duodenum

To investigate changes in vasoactive intestinal polypeptide (VIP) and corticotrophin releasing factor (CRF) in the plasma and duodenum of chronic stress-induced depressed rats and the effects of fluoxetine hydrochloride (fluoxetine) treatment on depression-induced changes in VIP and CRF. A Sprague-Dawley rat model of chronic stress-induced depression was produced. Thirty experimental rats were randomly divided into the following groups: control group, saline-treated depressed group, and fluoxetine-treated depressed group. Open-field testing was performed to assess the rats' behavior. VIP and CRF levels in plasma were measured by ELISA. Immunofluorescence techniques combined with laser scanning confocal microscopy (LSCM) were used to investigate VIP and CRF expression in the duodenum. The open-field behavior, both crossing and rearing, of depression model rats, decreased significantly compared with those of normal control rats over 5 min. Defecation times increased significantly. Compared to the control group, FITC fluorescence of duodenal CRF expression and plasma CRF levels in the depressed rats increased significantly (fluorescence intensity of duodenal CRF: 11.82 +/- 2.54 vs 25.17 +/- 4.63; plasma CRF: 11.82 +/- 2.54 ng/L vs 25.17 +/- 4.63 ng/L, P < 0.01), whereas duodenal VIP expression and plasma VIP levels decreased significantly (fluorescence intensity of duodenal VIP: 67.37 +/- 18.90 vs 44.51 +/- 16.37; plasma VIP: 67.37 +/- 18.90 ng/L vs 44.51 +/- 16.37 ng/L, P < 0.01). Fluoxetine improved depressed behavior, increased VIP expression and decreased CRF expression in plasma and the duodenal tissue of depressed rats. Chronic stress can induce injury to the duodenum, accompanied by increasing CRF and decreasing VIP in the plasma and duodenum. Treatment with fluoxetine can ameliorate pathological changes in the duodenum of depressed rats, which suggests that antidepressants are an effective therapeutic agent for some duodenal diseases caused by chronic stress. VIP is a potential therapeutic strategy.

Effects of Pirenzepine on Dai-kenchu-to-Induced Elevation of the Plasma Neuropeptide Levels in Humans

Dai-kenchu-to has been used for the treatment of abdominal obstructions, including bowel obstructions and a feeling of coldness in the abdomen. We reported that Dai-kenchu-to increases plasma neuropeptide [motilin, vasoactive intestinal polypeptide (VIP), serotonin, calcitonin gene-related peptide (CGRP), and substance P]-like immunoreactive substances (IS) levels and that its pharmacologic effects on the gastrointestine are due to changes in gastrointestinal mucosa-regulatory peptide levels. We examined the effects of the selective M(1) muscarinic receptor antagonist pirenzepine on the elevation of Dai-kenchu-to-induced plasma neuropeptide (gastrin, motilin, somatostatin, VIP, CGRP, substance P)-IS levels in human volunteers and the area under the plasma neuropeptide concentration-time curve from 0 to 240 min (AUC(0-->240 min)), which were calculated from the plasma neuropeptide concentration-time curves from each volunteers. Oral pretreatment with pirenzepine reduced the Dai-kenchu-to-induced elevation of plasma motilin and VIP-IS levels and AUC(0-->240 min). Combined treatment with Dai-kenchu-to and pirenzepine increased plasma somatostatin-IS levels and decreased plasma gastrin-IS levels and had no effects on plasma CGRP- and substance P-IS levels and AUC(0-->240 min) compared with administration of Dai-kenchu-to alone. Dai-kenchu-to appeared to induce the release of motilin and VIP into plasma mainly through the activation of M(1) muscarinic receptors, and pirenzepine may affect the pharmacologic action of Dai-kenchu-to by elevation of plasma motilin and VIP levels.

Effects of psychological stress on small intestinal motility and expression of cholecystokinin and vasoactive intestinal polypeptide in plasma and small intestine in mice

To investigate the effects of psychological stress on small intestinal motility and expression of cholecystokinin (CCK) and vasoactive intestinal polypeptide (VIP) in plasma and small intestine, and to explore the relationship between small intestinal motor disorders and gastrointestinal hormones under psychological stress. Thirty-six mice were randomly divided into psychological stress group and control group. A mouse model with psychological stress was established by housing the mice with a hungry cat in separate layers of a two-layer cage. A semi-solid colored marker (carbon-ink) was used for monitoring small intestinal transit. CCK and VIP levels in plasma and small intestine in mice were measured by radioimmunoassay (RIA). Small intestinal transit was inhibited (52.18+/-19.15% vs 70.19+/-17.79%, P<0.01) in mice after psychological stress, compared to the controls. Small intestinal CCK levels in psychological stress mice were significantly lower than those in the control group (0.75+/-0.53 microg/g vs 1.98+/-1.17 microg/g, P<0.01), whereas plasma CCK concentrations were not different between the groups. VIP levels in small intestine were significantly higher in psychological stress mice than those in the control group (8.45+/-1.09 microg/g vs 7.03+/-2.36 microg/g, P<0.01), while there was no significant difference in plasma VIP levels between the two groups. Psychological stress inhibits the small intestinal transit, probably by down-regulating CCK and up-regulating VIP expression in small intestine.

Systemic and cavernous plasma levels of vasoactive intestinal polypeptide during sexual arousal in healthy males.

Results from basic research scrutiny indicate a role for non-adrenergic, non-cholinergic transmitters, among which there are various peptides, in the physiology of normal male sexual function. Nevertheless, it is not yet known which particular peptides are essentially involved in maintaining sexual arousal and regulating penile tumescence and rigidity in adult males. Vasoactive intestinal polypeptide (VIP), a peptide with smooth muscle relaxing properties, is considered to be one of the factors that contributes to such control. The present study was performed to evaluate the significance of VIP in normal male sexual function. We determined the plasma levels of VIP in the systemic and cavernous blood of 54 healthy adult male volunteers, who were exposed to visual and tactile erotic stimuli in order to elicit penile tumescence and erection. Whole blood was aspirated from the corpus cavernosum and the cubital vein during penile flaccidity, tumescence, rigidity and detumescence, and VIP was quantified in plasma aliquots by means of a radioimmunoassay. Of the 54 volunteers, 16 were permitted to masturbate and ejaculate, and blood was then again withdrawn from the cavernous meshwork and the cubital vein in order to measure VIP. All VIP levels were registered within the normal physiological range from 3.0-30 pmol/l. No increase in median VIP plasma levels was observed in the systemic and cavernous blood when the flaccid penis became rigid. During penile detumescence, mean cavernous VIP level increased to 11.9+/-7.8 pmol/l (baseline: 8.6+/-3.0 pmol/l), whereas VIP remained unaltered in the systemic circulation. Following ejaculation, mean VIP level in the cavernous blood was elevated to 25.3+/-10.9 pmol/l, whereas, in the systemic blood, no significant changes were registered. Our results support the hypothesis that VIP plays a functional role in the mechanism of male sexual arousal. Nevertheless, our data indicate that the peptide is not the main non-adrenergic, non-cholinergic mediator of penile tumescence and rigidity in human males.

Distal stomach appears essential in the regulation of gastrointestinal transit.

Stomach and small bowel both influence gastrointestinal motility. We studied which portion of the stomach was essential for the regulation of gastrointestinal movement and determined the role of vasoactive intestinal polypeptide in this regulation. The study subjects consisted of 45 controls, 46 patients after subtotal gastrectomy, and 13 patients after total gastrectomy for stomach cancer. Orocecal transit time was measured, using the hydrogen breath test, to represent gastrointestinal movement, while plasma vasoactive intestinal polypeptide level was simultaneously assessed. The orocecal transit times in the study groups were (means +/- SD) 91.1 +/- 45.0, 57.1 +/- 34.3, and 60.8 +/- 34.8 min, respectively (P < 0.01). In the subtotal gastrectomy patients, age showed a negative correlation with orocecal transit time (r = -0.388; P < 0.01). In the total gastrectomy patients, no particular demographic factor influenced orocecal transit. Plasma vasoactive intestinal polypeptide levels in the three groups were 20.7 +/- 10.8, 22.7 +/- 10.9, and 20.6 +/- 9.1 pg/ml, respectively (NS). We conclude that both types of gastrectomies enhanced gastrointestinal movement, showing a similar effect, and that the distal stomach plus pylorus are most likely to exert an important inhibitory mechanism in the regulation of this movement. Vasoactive intestinal polypeptide is not a major peptide mediating this regulation.

Vasoactive Intestinal Polypeptide (VIP) Secretion and Refractory Diarrhea in Patients with AIDS or AIDS-Related Complex (ARC)

Elevated plasma levels of vasoactive intestinal polypeptide (VIP) (as assessed by a radio-immunoassay), were found in 7/11 patients with AIDS or AIDS-related Complex (ARC), evaluated because of prolonged intractable diarrhea with either an infectious (6 cases) or a non-infectious (5 cases) etiology. Six subjects have been treated with the somatostatin analogue octreotide, which gave both a favourable clinical response and a significant reduction in plasma VIP concentrations. Evaluation of plasma VIP levels may provide a pathophysiological basis for explaining the efficacy of octreotide therapy in HIV-infected patients suffering from both infectious and non-infectious refractory diarrhea.

Elevated Venous Concentrations of Vasoactive Intestinal Polypeptide in Cord Blood of Infants with Fetal Distress

Concentrations of vasoactive intestinal polypeptide (VIP) in cord plasma were determined in 70 neonates (birth weight, mean +/- SD, 3,213.5 +/- 50.9 g, gestation 39.5 +/- 0.2 weeks), 22 of whom had fetal distress. Arterial VIP levels in cord blood were not significantly different between infants with and without fetal distress. The mean venous VIP in cord blood of distressed infants (28.1 +/- 8.4 pg/ml, mean +/- SE) was significantly (p < 0.05) higher than that of normal neonates (12.6 +/- 3.4 pg/ml). The mean placental content of VIP was 5.1 +/- 0.3 ng/g wet tissue, although a correlation with the venous concentration in the cord was not demonstrated. Venous VIP levels were elevated 24 h after birth (34.6 +/- 13.7 pg/ml) and decreased on the 5th day of life to 12.9 +/- 3.8 pg/ml, which was not significantly different from the mean VIP level in childhood (14.7 +/- 3.1 pg/ml). These results demonstrate that, in the perinatal period, plasma VIP levels are elevated on two occasions: at delivery associated with fetal distress (cord vein), and at 24 h of age. VIP in the former seems to be of placental and/or maternal origin.

Plasma Vasoactive Intestinal Polypeptide in the Newborn Infant

Vasoactive intestinal polypeptide (VIP) has been suggested as a possible contributor to the development of gastrointestinal problems. VIP is produced by nerve endings in the intestinal tract and appears to have marked effects on gut motility and its blood flow. Since necrotizing enterocolitis and feeding intolerance are common problems in the newborn, we examined the plasma VIP responses to feeding in healthy preterm and term newborn infants. Plasma VIP levels were measured in 20 full‐term newborn infants (gestation of 39.4 ± 0.9 weeks, mean ± SD, and weight of 3,351 ± 477 g) and 38 preterm infants (gestation of 27–35 weeks, weight of 920–2,440 g). In term infants, cord blood samples were obtained from the umbilical artery and vein and then before and after the feed. For preterm infants, blood samples were obtained prior to the introduction of oral feeds during the first week, and then before and after feeding once a week over the next 4 weeks. Feeding ranged from diluted premature formula to special care (24 calories per ounce) for the preterm, and breast milk or regular commercial formula for the term infants. Twenty‐one healthy adults, age 25–42 years, were studied for comparison. In the term newborn infants, the plasma VIP levels in the umbilical venous blood were lower, although not statistically significant (p = 0.06), than the umbilical arterial blood (10.78 ± 5.89 vs. 13.54 ± 6.71 pmol/L), suggesting placental metabolism of VIP. After birth, there was a significant increase in plasma VIP levels (18.89 ± 10.07 pmol/L, p = 0.001). Introduction of formula or human milk did not cause any change in circulating VIP levels. The plasma VIP levels in the term newborn infants were significantly (p = 0.001) higher than those observed in normal adults (18.89 ± 10.07 vs. 6.04 ± 2.30 pmol/L). In the preterm infants, VIP levels during fasting were significantly lower (13.56 ± 8.67 pmol/L, p = 0.05) than those observed in term infants. There was a small statistically significant (p = 0.01) increase in VIP levels in the preterm infants during the second (17.41 ± 10.42 pmol/L) and third (16.63 ± 9.27 pmol/L) weeks after the introduction of feedings. The significance of the higher VIP levels in the newborn infants remains unknown. Because no infants developed gastrointestinal intolerance, no correlation between VIP levels and gastrointestinal problems could be demonstrated.

Plasma Vasoactive Intestinal Polypeptide in the Newborn Infant

Vasoactive intestinal polypeptide (VIP) has been suggested as a possible contributor to the development of gastrointestinal problems. VIP is produced by nerve endings in the intestinal tract and appears to have marked effects on gut motility and its blood flow. Since necrotizing enterocolitis and feeding intolerance are common problems in the newborn, we examined the plasma VIP responses to feeding in healthy preterm and term newborn infants. Plasma VIP levels were measured in 20 full-term newborn infants (gestation of 39.4 +/- 0.9 weeks, mean +/- SD, and weight of 3,351 +/- 477 g) and 38 preterm infants (gestation of 27-35 weeks, weight of 920-2,440 g). In term infants, cord blood samples were obtained from the umbilical artery and vein and then before and after the feed. For preterm infants, blood samples were obtained prior to the introduction of oral feeds during the first week, and then before and after feeding once a week over the next 4 weeks. Feeding ranged from diluted premature formula to special care (24 calories per ounce) for the preterm, and breast milk or regular commercial formula for the term infants. Twenty-one healthy adults, age 25-42 years, were studied for comparison. In the term newborn infants, the plasma VIP levels in the umbilical venous blood were lower, although not statistically significant (p = 0.06), than the umbilical arterial blood (10.78 +/- 5.89 vs. 13.54 +/- 6.71 pmol/L), suggesting placental metabolism of VIP. After birth, there was a significant increase in plasma VIP levels (18.89 +/- 10.07 pmol/L, p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Elevated VIP and endotoxin plasma levels in human gram-negative septic shock

Vasoactive intestinal polypeptide (VIP) and endotoxin (lipopolysaccharides, LPS) were measured in plasma samples from 11 patients with bacteriologically verified meningococcal disease. Five patients suffered fulminant septicaemia, developed severe septic shock, and 2 died due to circulatory collapse. Initially, all 5 had levels of VIP above 4 pM and plasma endotoxin above 200 ng/liter. Five patients were diagnosed as meningitis and 1 as having meningococcaemia, all with a normal circulatory state. None of these 6 patients had initially levels of VIP above 2.5 pM or endotoxin levels above 25 ng/liter ( P < 0.001). A correlation existed between plasma endotoxin and VIP levels ( r = 0.735, P = 0.01). Sequentially collected samples from 3 patients showed rapidly declining VIP levels after initiation of antibiotic and fluid treatment. These results are in agreement with previous animal experiments, suggesting that endotoxin directly or indirectly stimulates the VIP-ergic nervous system in the initial phase of gram-negative septic shock in man.

Plasma somatostatin and vasoactive intestinal polypeptide responses to an oral mixed test meal in obese patients.

Ten obese and 10 control subjects were studied in basal conditions and after ingestion of a standard mixed test meal. Blood glucose, insulin, somatostatin (SLI) and vasoactive intestinal polypeptide (VIP) concentrations were determined before and 30, 60, 90, 120, 180 and 240 min after the start of the meal. Basal SLI levels in the obese (14.4 +/- 0.7 ng/l) were not significantly different from those in the controls (15.5 +/- 0.8 ng/l), whereas after the meal a blunted secretory response was recorded. Baseline plasma VIP levels were higher in the obese (29.7 +/- 1.5 ng/l) than in the control subjects (19.8 +/- 1.3 ng/l) and, similarly to the controls, were unaffected by meal ingestion. Data suggest that in the course of obesity an enhanced VIP secretion in association with a diminished SLI responsiveness to meals occurs.

Brain-gut peptides in sauna-induced hyperthermia.

The release of brain-gut peptides during sauna bathing was studied in seven women. All women underwent a 20 min sauna bath. Their sublingual temperature rose from 36.9 +/- 0.1 degrees C to 38.6 +/- 0.2 degrees C (mean +/- SEM). A significant increase in circulating plasma vasoactive intestinal polypeptide (VIP) was observed during heat exposure, whereas plasma pancreatic polypeptide (PP), motilin and blood glucose rose and stayed significantly elevated first during the ensuing 60 min (P less than 0.05 in all cases). A similar increase in plasma insulin failed to reach statistical significance, whereas the plasma levels of somatostatin and cholecystokinin (CCK) remained unchanged. It is suggested that the plasma VIP levels are related to compensatory mechanisms during heat exposure with vasodilatation and heat loss.

Vipoma syndrome

Since the description of the watery diarrhea syndrome by Verner and Morrison 29 years ago, clinical and experimental observations have elucidated the pathophysiology of this disease. Vasoactive intestinal polypeptide (VIP) is produced and released by a tumor of the pancreatic islets or by a tumor of neural crest origin such as a ganglioneuroma. Under normal conditions, current evidence suggests that VIP is a neurotransmitter in the central and peripheral nervous systems and particularly in the peptidergic nervous system. The low VIP plasma concentration observed in healthy subjects is viewed as a neuronal overflow since it has been impossible to ascertain any endocrine role for circulating VIP. Markedly elevated VIP plasma levels in the VIPoma syndrome lead to intestinal secretion with severe secretory diarrhea, resulting in hypovolemia, hypokalemia, and acidosis. These symptoms subside after successful tumor removal. Approximately 50 percent of patients have metastatic spread at the time of diagnosis. For these patients, a new and promising therapeutic modality is available in the form of a subcutaneously administered somatostatin analogue that relieves symptoms through potent inhibition of VIP release from tumor tissue.

Vasoactive intestinal polypeptides in connective tissue massage. With a note on VIP in heat pack treatment

1. 1. The vasoactive intestinal polypeptide (VIP) is a powerful dilatator in a number of vascular beds. Plasma VIP is increased in active physical exercise and in transcutaneous nerve stimulation. 2. 2. Plasma VIP has in this study been measured during other physiotherapeutic procedures causing skin vasodilatation, such as connective tissue massage and heat packs. 3. 3. Plasma VIP levels and skin temperature of fingers and toes were measured in 12 patients before and at various intervals following a 30 min connective tissue massage. 4. 4. No significant increase in the plasma VIP was found. The same was true in a pilot study using heat pack treatment. 5. 5. It is suggested that somehow VIP is more involved in the vascular response to active physical activity and peripheral nerve stimulation than to passive procedures like connective tissue massage and heat pack treatment.

Increase in plasma vasoactive intestinal polypeptide (VIP) in muscular exercise in humans

1. 1. We have previously shown that plasma vasoactive intestinal polypeptide (VIP) is increased in normal subjects by low-frequency transcutaneous nerve stimulation. The latter may also increase short-term physical performance in athletes (running, swimming and ergometer cycling). 2. 2. The present study examines whether the plasma VIP level is similarly increased in short-term ergometer exercise in seven healthy volunteers. 3. 3. A group of four patients with angina pectoris were included, since a lowered concentration of VIP is found in diseased heart tissue. 4. 4. In the group of healthy subjects, ergometer exercises with progressive increases in workload until exhaustion, lasting from 16 to 32 min (mean 26 min) and with a corresponding maximum energy output of 1500 to 5100 W (mean 3560 W), resulted in an increase in plasma VIP concentration from a pre-stimulatory level of 3.3 pmol·1 −1 to 5.3, 5.2 and 5.6 pmol·1 −1, measured 3, 10 and 20 min respectively, following termination of the exercise, i.e. a maximal 70% increase. 5. 5. In the patients with angina pectoris there was no significant VIP increase (cycling time 7–15 min, work performed 400–1350 W). 6. 6. Possible triggering mechanisms for VIP release and its source are discussed.