Plasma Vasoactive Intestinal Peptide Research Articles

Effects of portal vein stenosis and superior mesenteric vein ligation on mesenteric venous pressure and porta-systemic shunting in the rat.

We studied the relative contributions of splanchnic congestion and porta-systemic shunting to the maintenance of experimental portal venous hypertension. Three groups of rats were prepared: portal vein-stenosed, superior mesenteric vein-ligated and sham operated. Though elevated in both operated groups compared to controls, mesenteric venous pressure was highest in the portal vein-stenosed animals (PV vs SMV vs Sham: 19.6 +/- 1.3 vs 15.6 +/- 0.7 vs 13 +/- 0.6; p < .05 PV and SMV vs Sham, and PV vs SMV) despite the presence of 50% porta-systemic shunting in the portal vein-stenosed animals. Shunting was negligible in the other two groups. Peripheral plasma glucagon and vasoactive intestinal peptide (VIP) levels were similar in all three groups. We conclude that mesenteric congestion alone plays a minor role in the pathogenesis of portal hypertension, which may instead be related to the porta-systemic shunting of vasoactive substances other than glucagon and VIP.

Atrial natriuretic peptide in pregnancy: response to oral sodium supplementation.

1. The control of extracellular fluid volume (ECFV) in normal pregnancy may be related to changes in atrial natriuretic peptide. Previous studies in non-pregnant subjects have suggested that plasma atrial natriuretic peptide (ANP) increases in response to dietary sodium supplementation because of an increase in plasma volume, although this has not been measured directly. 2. Nine women who were pregnant in the third trimester undertook oral sodium supplementation (136 mmol) for 5 days in addition to their usual diet. Twenty-four hour urinary sodium excretion increased by 125 +/- 54 mmol/day (mean +/- s.d.; P less than 0.01). Plasma volume was unchanged, although total ECFV tended to increase (P less than 0.09 and bodyweight increased (1.3 +/- 1.4 kg; P less than 0.01) at the end of these diets. 3. Plasma ANP increased by 30.7 [8.6, 34.5] pmol/L (median [25th, 75th percentile]; P less than 0.05), while plasma renin concentration decreased significantly from 7.3 [6.2, 11.2] to 2.6 [1.7, 3.9] pmol angiotensin I/mL (P less than 0.01), as did plasma aldosterone concentration (1435 [1162, 1722] to 753 [595, 1110] fmol/mL; P less than 0.01). Plasma vasoactive intestinal peptide was unchanged. 4. Pregnant women respond to increased dietary sodium with an increase in plasma ANP in the absence of a significant increase in plasma volume. The acute regulation of plasma ANP in response to increases in dietary sodium in pregnant women does not appear to be mediated by changes in intravascular fluid volume.

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.

Cholecystokinin, vasoactive intestinal peptide and peptide histidine methionine responses to feeding in anorexia nervosa

Anorexia nervosa (AN) is a syndrome of unknown cause characterized by voluntary starvation. Cholecystokinin has been implicated as a neuroendocrine regulatory factor in control of satiety. Relatively little information is known about gastrointestinal hormone responses to feeding in subjects with anorexia nervosa. In the present studies, we examine fasting and postprandial levels of cholecystokinin (CCK), vasoactive intestinal peptide (VIP) and peptide histidine methionine (PHM) in anorexia nervosa subjects and in control individuals. Results of these studies indicate that plasma CCK response to a liquid meal (Ensure Plus) in untreated AN subjects was distinctly different from that observed in healthy controls, both in terms of temporal pattern of peptide released and the amount of CCK secreted into the circulation. Peak levels of CCK release occurred at 30 min following meal ingestion in AN patients and at 60 min in control subjects. Integrated CCK release in untreated AN patients was approximately twice that measured in control individuals. Renutrition therapy was associated with reversion of the pattern of CCK release to that observed in control subjects. Plasma VIP levels were unchanged following meal ingestion in both control and anorexic subjects. In contrast, PHM levels in AN subjects were significantly greater than that observed in control individuals. The pattern of PHM release following liquid meal ingestion was similar to that observed with plasma CCK; namely, peak release of peptide was observed at 30 min which was significantly greater than corresponding control values ( P < 0.05). In conclusion, these results demonstrate distinctive differences in plasma CCK and PHM levels in response to feeding in AN subjects when compared to control individuals. These findings suggest that the earlier and greater rise in plasma CCK levels in AN subjects following meal ingestion may contribute to the abnormal sensation of satiety in this condition.

Effects of Hachimijiogan on Dopamine, Serotonin and Vasoactive Intestinal Peptide in Plasma and Hypothalamus in Sulpiride – Induced Hyperprolactinemic Rats

Effect of Hachimijiogan (HJ) on dopamine (DA), serotonin (5-HT) and vasoactive intestinal peptide (VIP) was examined in plasma and hypothalamic tissue of sulpiride-induced hyperprolactinemic rats (SHR). Similar to bromocriptine (BR), HJ, in combination with sulpiride, suppressed plasma prolactin levels raised by sulpiride alone. Furthermore, HJ, together with sulpiride, increased plasma DA levels decreased by sulpiride alone, while 5-HT in plasma was increased by sulpiride and HJ, individually or in combination. However, plasma VIP levels were under detection limits on some occasions after HJ treatment. Successively, DA, 5-HT and VIP levels in the hypothalamus were determined. Similar to the effect caused by BR, DA and 5-HT levels in hypothalamic tissue reduced by sulpiride alone were also significantly increased by HJ together with sulpiride, while VIP levels were sometimes under detection levels with or without HJ. These results suggest that HJ stimulates the hypothalamus to increase DA and 5-HT in SHR, providing evidence for the clinical efficiency of HJ in combating hyperprolactinemia. The effect of HJ on VIP in plasma or hypothalamic tissue is, however, questionable.

Plasma vasoactive intestinal polypeptide concentration determination in patients with diarrhea

Determination of plasma levels of vasoactive intestinal polypeptide (VIP) has been used for screening patients with chronic diarrhea to identify potential neuroendocrine tumors. This 6-year blinded study from 1981 to 1986 examines the causes of elevated VIP levels in patients. In healthy volunteers (n = 144), VIP concentrations ranged from 14 to 76 pg/mL (mean ± SE, 28 ± 12), whereas in chronic renal failure, 4 of 34 patients or 12% [serum creatinine 4.5–9.0 mg/dL (397–795 μmol/L)] had an elevation to > 100 pg/mL. No patient with idiopathic hepatic cirrhosis (n = 12) had elevation of serum concentration of this peptide. Among 588 consecutive unselected patients undergoing evaluation for chronic diarrhea (n = 362; 62%) or possible neuroendocrine tumor (n = 214; 36%), 23 patients (3.9%) had concentrations >76 pg/mL. In this group, 5 patients had functioning (VIP, 160–5975 pg/mL) and 5 had nonfunctioning (VIP, 80–120 pg/mL) pancreatic islet cell carcinomas: all 10 patients had hepatic metastases. Other known causes of elevated levels of VIP, ranging from 80 to 340 pg/mL, included other neurogenic tumors (n = 3), small- bowel resection (n = 2), inflammatory bowel disease (n = 2), chronic renal failure (n = 1), and prolonged fasting (n = 1). Patients with diarrhea in which VIP-secreting tumors were identified had plasma vasoactive intestinal peptide concentrations >140 pg/mL. In patients with chronic diarrhea, determination of plasma vasoactive intestinal peptide levels did identify tumors secreting this peptide, but the results from this referral institution did not show identification of these tumors early in their clinical course.

Preferential Increase in Pituitary Prolactin Versus Vasoactive Intestinal Peptide as a Function of Estradiol Benzoate Dose in the Ovariectomized Rat*

Vasoactive intestinal peptide (VIP) is synthesized in various tissues, including the anterior pituitary gland, where it may stimulate the release of PRL. Because estrogen plays a central role in the regulation of PRL, it becomes important to determine the effects of this steroid on both pituitary VIP and PRL. To study this, pituitary VIP and PRL and plasma PRL were assayed in ovariectomized rats after treatment with estradiol benzoate (EB; 0.007, 0.07, 0.7, 7 or 70 microgram/rat). Pituitary and plasma TSH were also determined as well as VIP content in the medial basal hypothalamus, suprachiasmatic region, cerebral cortex, and jejunum. Oil-treated rats served as controls. Injection of 0.7 or 7 microgram EB resulted in a significant increase in pituitary PRL without changing plasma PRL levels or pituitary VIP content compared to values in the control group. Only treatment with 70 microgram EB produced a significant increase in both pituitary VIP and PRL as well as in plasma PRL compared to control values. EB treatment at any of the doses used had no significant effect on pituitary and plasma TSH or VIP content in any of the other tissues examined. These data show that pituitary PRL and VIP are differentially regulated in response to estrogen. The increases in pituitary VIP and basal plasma PRL after treatment with the highest dose of EB suggest that pituitary VIP may be involved in the development of estrogen-induced hyperprolactinemia. These data also show that the regulations of pituitary VIP and TSH are independent of each other in the estrogen-treated rat.

Suckling-Induced Changes of Vasoactive Intestinal Peptide Concentrations in Hypothalamic Areas Implicated in the Control of Prolactin Release

The present study was designed to investigate whether the vasoactive intestinal peptide (VIP) concentration in hypothalamic nuclei, dorsal raphe nucleus (DR) and pituitary lobes of lactating rats changes in physiological situations when prolactin (PRL) secretion is stimulated (suckling) or inhibited (pup separation). In addition VIP levels in blood plasma were determined in both situations. Acute suckling induced changes in VIP concentration only in the rostral part of the anterior hypothalamic (rAHN) and the paraventricular (PVN) nuclei of all the brain areas examined. VIP concentration in the rAHN increased at 5 min from 3.52 +/- 0.30 (mean +/- SEM) to 8.67 +/- 1.91 ng/mg protein (p less than 0.05) but fell to baseline values after 30 min suckling (p less than 0.05; 5 vs. 30 min). Although changes in VIP concentration in the suprachiasmatic nucleus (SCN) did not attain statistical significance, they followed the same trends as the changes of VIP in the rAHN. The opposite pattern of changes was observed in the PVN with a decrease in VIP concentration following 5 min suckling (p less than 0.01). At 30 min the VIP values showed a trend towards 0-min values. Pup removal did not affect VIP concentrations in the rAHN, PVN, SCN, median eminence, supraoptic nucleus and DR. VIP values were not detectable in the arcuate nucleus in any of the experimental situations examined. Lactation increased VIP concentration only in the rAHN and PVN when lactating rats with their pups were compared with virgin female diestrous rats. VIP concentration in the anterior lobe of the pituitary from lactating rats did not change with pup separation or suckling.(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of Vascoactive Intestinal Peptide Release and Metabolism by Sodium

To determine whether vasoactive intestinal peptide (VIP) might act as a humoral mediator for a proposed portal or hepatic sodium monitor, we measured plasma VIP levels and urinary sodium excretion after portal and intravenous sodium loading in rabbits equilibrated on normal and low sodium diets. Sodium excretion was significantly less after intravenous (2 h: p less than 0.005; 4 h; p less than 0.005; 8 h; p less than 0.025) than after portal sodium administration in rabbit on a low-sodium diet. Plasma VIP levels fell after intravenous (p less than 0.005) but not after intraportal sodium in this group. To determine whether this fall in VIP levels reflected increased metabolism or decreased secretion, metabolic clearance studies were performed in rabbits on a low sodium diet. The metabolic clearance rate of VIP and its theoretical secretion rate increased after intravenous sodium loading in rabbits on a low salt diet (MCR, p less than 0.025; SR, p less than 0.05). We conclude, therefore, that in rabbits on a low-salt diet, intravenous sodium increases VIP metabolism, causing a decrease in plasma levels that may explain the difference in sodium excretion.

Regulation of Vascoactive Intestinal Peptide Release and Metabolism by Sodium

To determine whether vasoactive intestinal peptide (VIP) might act as a humoral mediator for a proposed portal or hepatic sodium monitor, we measured plasma VIP levels and urinary sodium excretion after portal and intravenous sodium loading in rabbits equilibrated on normal and low sodium diets. Sodium excretion was significantly less after intravenous (2 h: p < 0.005; 4 h: p < 0.005; 8 h: p 0.025) than after portal sodium administration in rabbit on a low-sodium diet. Plasma VIP levels fell after intravenous (p < 0.005) but not after intraportal sodium in this group. To determine whether this fall in VIP levels reflected increased metabolism or decreased secretion, metabolic clearance studies were performed in rabbits on a low sodium diet. The metabolic clearance rate of VIP and its theoretical secretion rate increased after intravenous sodium loading in rabbits on a low salt diet (MCR, p < 0.025; SR, p < 0.05). We conclude, therefore, that in rabbits on a low-salt diet, intravenous sodium increases VIP metabolism, causing a decrease in plasma levels that may explain the difference in sodium excretion.

Sodium depletion decreases hepatic metabolism of vasoactive intestinal peptide in the rabbit.

1. Reports that a greater natriuresis occurs after gastric rather than intravenous sodium loads suggest that a gastric sodium monitor exists which releases a humoral natriuretic factor. As vasoactive intestinal peptide (VIP) is natriuretic, it might act as this mediator. To determine whether it released from the gut in response to sodium we measured VIP levels in portal and systemic plasma of anaesthetized rabbits after a gastric sodium load. Levels of VIP in systemic plasma were also measured in conscious rabbits after gastric and portal sodium loads to determine the contributions of anaesthesia or increased sodium concentration in the portal tract to any observed rise in systemic VIP levels. 2. In the anaesthetized rabbit study portal and systemic VIP levels had both increased significantly from control values by 5 min after the sodium load in the low salt diet group (P less than 0.025, portal: P less than 0.05, systemic). By 10 min the levels in systemic and portal plasma were equal. 3. In the conscious rabbits an increase in systemic VIP levels was observed in the group on a low salt diet after a gastric but not a portal sodium load. 4. We conclude that VIP is released in response to gastric sodium loads in rabbits on low salt diets and that hepatic metabolism of VIP is reduced in this group.

Vasoactive intestinal peptide as a laboratory supplement to clinical activity index in inflammatory bowel disease.

Circulating levels of vasoactive intestinal peptide (VIP) in plasma were measured in gauging activity in inflammatory bowel disease (IBD). One hundred-fifteen adult IBD patients were studied cross-sectionally and prospectively, 48 with ulcerative colitis (UC) and 67 with Crohn's disease (CD). Sequential samples of plasma were assayed for VIP by specific radioimmunoassay. Sixty males and 55 females, ranging in age from 22 to 76 years were studied over six months. The results revealed a strong, positive association between VIP levels and clinical activity, both at baseline (r = 0.38, P less than 0.001) and follow-up (r = .41, P less than 0.001). The ability of the VIP immunoassay to gauge clinical activity was also evaluated where VIP concentrations above 30 pg/ml were defined as abnormal. At baseline, sensitivity (specificity) was found to be 81% (55%). The predictive value of a positive (negative) test was 57% (80%). These estimates did not differ at follow-up. Examination of paired plasma samples from intermittently active patients revealed nearly twofold increases (P less than 0.05) in VIP concentration during active periods of disease. The data suggest that plasma VIP levels may be a valuable laboratory parameter in gauging activity in inflammatory bowel disease.

A Case of the Watery Diarrhea-Hypokalemia-Achlorhydria Syndrome: Successful Preoperative Treatment of Watery Diarrhea with a Somatostatin Analogue

A 35-year-old man presenting with severe watery diarrhea was diagnosed as having the watery diarrhea, hypokalemia and achlorhydria (WDHA) syndrome with the elevation of plasma vasoactive intestinal peptide (VIP) level. Imaging diagnostic techniques revealed a hypervascular tumor at the tail of the pancreas as well as a solitary liver metastasis. During the patient's stay in hospital, he developed acute renal failure probably due to persistent dehydration and severe hypokalemia. Although these complications improved with artificial dialyses, severe watery diarrhea continued, which made it difficult to achieve surgical resection of the tumor. A new long-acting and potent somatostatin analogue, SMS 201-995 (Sandoz Ltd, Basel, Switzerland), was tested and was shown to be effective; after a few hours of subcutaneous injection of this agent, the watery diarrhea disappeared, which in turn improved the patient's hypokalemia, hypercalcemia and metabolic acidosis. Three weeks later, distal pancreatectomy with splenectomy and hepatic lobectomy were successfully performed, and the patient resumed his normal life. The somatostatin analogue has been reported to be useful in the long-term treatment of patients with inoperable WDHA syndrome. The present case demonstrated that short-term administration of this agent is also useful for improving the condition of WDHA patients at the preoperative stage.

Effect of nasal allergen challenge on serotonin, substance P and vasoactive intestinal peptide in plasma and nasal secretions

We have studied the changes in concentration of serotonin, substance P, and vasoactive intestinal peptide (VIP) in plasma following a nasal allergen provocation in 14 grass pollen-allergic subjects; in five the urinary excretion of serotonin and 5-hydroxy-indolyl-acetic acid (5-HIAA) was also measured. In addition, the concentration of serotonin and substance P was measured in nasal secretions following nasal challenge with allergen and methacholine. The results showed an allergen-induced increase in free plasma serotonin (P less than 0.01) and no change in platelet serotonin, urinary serotonin and urinary 5-HIAA. The plasma substance P level tended to fall (P greater than 0.1), while plasma VIP increased significantly (P less than 0.02). In nasal secretions, there were measurable levels of serotonin in all samples and of substance P in all but one. There was no difference between the concentrations of serotonin and substance P in secretions collected after allergen challenge and after methacholine challenge. For both substances, the secretion median value was comparable to that of plasma. Symptom reduction by topical and systemic pretreatment with a serotonin- and VIP-antagonist before nasal allergen provocation is necessary to define the role of these two agents in allergic rhinitis.

Receptors for vasoactive intestinal peptide (VIP) on human mononuclear leucocytes are upregulated during prolonged strain and energy deficiency

VIP receptors on blood mononuclear leucocytes and plasma VIP concentrations were studied during a ranger training course lasting for five days with almost continuous physical activity, and energy deficiency. The maximum binding capacity (Bmax) for the high affinity receptor increased ( p<0.0005) from 0.71 (SEM=0.11, N=10) fmol/million cells to a maximum of 7.33 (SEM=1.0) fmol/million cells on Day 4. There was no significant change in the dissociation constant (Kd) for the high affinity receptor, and no effect on Kd nor Bmax for the low affinity VIP receptor was detected. Plasma VIP concentration increased ( p<0.0005) from 8.8 pmol/l (SEM=0.6) to a maximum of 23.4 (SEM=1.9) on the second day of the course. However, the highest plasma concentrations were about one order of magnitude lower than the dissociation constant (Kd) for the high affinity VIP receptor on the mononuclear leucocytes. These data indicate that heterologous upregulation of the high affinity VIP receptor on mononuclear blood cells takes place during combined strenuous physical exercise, and calorie deficiency.

Watery Diarrhea, Hypokalemia, Achlorhydria Syndrome in an Infant

An 8-week-old infant presented with vomiting and failure to thrive due to small bowel obstruction caused by a diffusely enlarged pancreas. Surgical bypass of the obstruction was followed by secretory diarrhea, hypokalemia, and dehydration. Plasma vasoactive intestinal peptide (VIP) (823pg/ml), pancreatic polypeptide (4,500 pg/ml), and neurotensin (680 pg/ml) concentrations were markedly elevated. No neoplastic process was identified. Therapy with the long-acting somatostatin analogue SMS 201-995 was followed by decline in VIP concentrations (900 to 200-300 pg/ml), decrease in stool frequency, and normalization of serum electrolytes. During 12 months of somatostatin analogue therapy, length and weight progressed along the 3rd percentile on the Tanner growth chart.

Watery Diarrhea, Hypokalemia, Achlorhydria Syndrome in an Infant

SummaryAn 8‐week‐old infant presented with vomiting and failure to thrive due to small bowel obstruction caused by a diffusely enlarged pancreas. Surgical bypass of the obstruction was followed by secretory diarrhea, hypokalemia, and dehydration. Plasma vasoactive intestinal peptide (VIP) (823 pg/ml), pancreatic polypeptide (4,500 pg/ml), and neurotensin (680 pg/ml) concentrations were markedly elevated. No neoplastic process was identified. Therapy with the long‐acting somatostatin analogue SMS 201–995 was followed by decline in VIP concentrations (900 to 200–300 pg/ml), decrease in stool frequency, and normalization of serum electrolytes. During 12 months of somatostatin analogue therapy, length and weight progressed along the 3rd percentile on the Tanner growth chart.

The plasma vasoactive intestinal peptide (VIP) response to exercise is increased after prolonged strain, sleep and energy deficiency and extinguished by glucose infusion

The VIP response to a 30 minute bicycle exercise test with a workload of 50% of VO2 max was investigated in young men before and after 5 days of continuous physical activities, almost total sleep deprivation and limited amounts of food. It was shown that plasma VIP increased during physical exercise lasting for more than 20 minutes with a workload of more than 50% of VO2 max. A further increase took place in the early recovery period to a maximum level 5-10 minutes after the exercise. This response to exercise is even stronger after prolonged strain. Glucose infusion during the exercise almost abolished the increase of plasma VIP.

Fundamental and clinical evaluation of vasoactive intestinal peptide (VIP) in pancreatitis by radioimmunoassay kit.

Plasma vasoactive intestinal peptide (VIP) concentrations of normal individuals and patients with pancreatitis were studied using a VIP RIA kit. The inter-assay and intra-assay variation of this kit were between 2.1 and 9.4%. The VIP levels increased in the acute phase of acute pancreatitis and patients with chronic pancreatitis. The VIP concentration increased during the first 30 min of glucose tolerance test, but this increase was much smaller than that in insulin. These results suggest that this kit is useful for physiologic and pathologic changes in the VIP level.