Plasma Vasoactive Intestinal Polypeptide Concentration Research Articles

Vasoactive intestinal polypeptide and the female genital tract: Relationship to reproductive phase and delivery

Recently, vasoactive intestinal polypeptide (VIP) has been localized in nerve fibers in the human female genital tract. In the present investigation, the effect and concentration of VIP was studied in uterine tissue from pregnant and nonpregnant women, and the plasma concentration of VIP was measured in relationship to diurnal rhythm, intake of food, menstrual cycle, pregnancy, labor, age, and sexual arousal. In vitro VIP inhibited the contractions of the nonpregnant but not of the pregnant uterus. The median concentration of VIP in myometrium from pregnant women (<0.1 pmole/gm) was significantly lower than that in myometrium from nonpregnant women (1.6 pmoles/gm). The venous plasma concentrations of VIP during labor (10.5 to 13.0 pmoles/L) were significantly higher than those during pregnancy (2.0 to 5.0 pmoles/L) and the menstrual cycle (4.7 to 6.5 pmoles/L), and after delivery (3.2 to 7.0 pmoles/L). The median venous concentration of VIP increased significantly during sexual arousal, from 4.0 to 8.5 pmoles/L. The median arterial and venous concentrations in the umbilical cord (12.5 and 14.5 pmoles/L, respectively) were significantly higher than the concentration in maternal peripheral venous blood (5.2 pmoles/L). The plasma concentrations of VIP were not related to intake of food, diurnal rhythm, menstrual cycle, or age. The conclusion is that the function of VIP may be related to pregnancy, delivery, and sexual stimulation.

Clinicopathological study of pancreatic and ganglioneuroblastoma tumours secreting vasoactive intestinal polypeptide (vipomas).

During a six-year period (1973-9) 52 patients with pancreatic tumours and 10 with ganglioneuroblastomas were found to have raised plasma vasoactive intestinal polypeptide (VIP) concentrations. All the patients had severe secretory diarrhoea, weight loss, dehydration, hypokalaemic acidosis, and a raised plasma urea concentration. Reduced gastric acid secretion was seen in 72% of patients. Plasma VIP concentrations were not raised in patients with diarrhoea due to other types of tumour or disease or in hormone-secreting tumours not associated with diarrhoea. Plasma VIP measurement may therefore give clinical guidance in a patient with persistent watery diarrhoea and hypokalaemic acidosis. Surgical excision was clearly the treatment of choice, but metastatic pancreatic tumours usually responded to streptozotocin.

Infusion of Vasoactive Intestinal Polypeptide in Man: Pharmacokinetics and Effect on Gastric Acid Secretion

Elimination and effect on acid secretion of vasoactive intestinal polypeptide (VIP) were studied in six healthy volunteers. On a background infusion of pentagastrin, 100 ng/kg-h, VIP was administered as stepwise intravenous infusions in doses of 0.5, 0.9, and 2.7 micro/g/kg-h, each dose being give for 1 h. Mean plasma VIP concentrations rose from 5.7 pmol/l to 28, 106 and 336 pmol/l during the VIP infusions. No significant changes in acid secretion occurred during VIP infusion as compared to infusion of pentagastrin alone, and no duodeno-gastric reflux was registered. Serum gastrin concentrations were unaltered during VIP infusion. Elimination of VIP was bi-exponential with half-lives of 2 and 21 min, respectively. Metabolic clearance rate was 42 ml/kg-min and the estimated volume of distribution 135 ml/kg.

Vasoactive intestinal polypeptide and the canine cerebral circulation.

A potential role for cerebrovascular nerves containing vasoactive intestinal polypeptide (VIP) was examined in 24 anesthetized, ventilated dogs. Cerebral blood flow (CBF) was measured by either the cerebral venous outflow or microsphere method. Plasma VIP concentration was measured by radioimmunoassay. Hypercapnia (5% and 10% CO2) and hypoxia (7% O2) produced significant increases in cerebral venous outflow, but had no affect on arterial or cerebral venous VIP concentrations. Measurements of VIP in cerebrospinal fluid (CSF) made during 5% and 8% CO2 breathing also were not different from control values. VIP produced large dose-dependent increases in common carotid artery and temporalis muscle blood flow when injected or infused intraarterially; however, VIP had no effect on total or regional cerebral blood flow (rCBF) within the brain when administered in a similar manner. Unilateral perfusion of the cerebral ventricles with VIP produced significant increases (range: 11-80%) in rCBF. These data are consistent with the possibility that local release of VIP from perivascular nerve endings could affect CBF. The unresponsiveness of canine cerebral vessels to blood-borne VIP may be due to the blood-brain barrier, since VIP dilates cerebral vessels when the barrier is bypassed by intraventricular infusion. These studies do not support the hypothesis that CBF changes induced during hypercapnia or hypoxia are mediated by VIP.

Increased myometrial blood flow evoked by vasoactive intestinal polypeptide in the non-pregnant goat.

1. The effect of vasoactive intestinal polypeptide (VIP) on myometrial blood flow was evaluated in anaesthetized goats. A solution of VIP, or vehicle alone, was infused into the right internal iliac artery for a period of 10 min. The myometrial blood flow in both uterine horns was measured from the third to the seventh min of the infusion by the gas clearance technique after local injection of (133)xenon in 10 mul. saline solution. Blood samples were collected from both utero-ovarian veins 5 min from the onset of the infusion and the plasma concentration of VIP determined by radio-immunoassay.2. During infusion of vehicle before VIP, myometrial blood flow was of the same magnitude in both uterine horns, i.e. 0.06-0.12 ml./min per g. The blood flow of the right horn increased to 0.20-0.39 ml./min per g during infusion of VIP (300 p-mole/min) in the ipsilateral artery, whilst that of the left horn rose to 0.13-0.26 ml./min per g. The effect was sometimes observed to last for more than 40 min.3. Increased myometrial blood flow was observed with infusion rates down to 3 p-mole/min. Once a response to VIP had been provoked, however, the vasculature sometimes became refractory to further stimulation.4. The plasma concentration of VIP increased in both utero-ovarian veins during unilateral infusion of the peptide.5. Methylene blue given through the infusion catheter stained tissue in both uterine horns, further evidencing that their blood supply is not entirely separate.6. Uterine motility was observed to diminish during the VIP infusions.7. During infusion of VIP (300 p-mole/min) heart rate rose from 146 +/- 6 to 158 +/- 7 beats/min. No significant change occurred in arterial blood pressure.8. It is concluded that the increase in blood flow is due to a local response and that, since VIP has been demonstrated in uterine nerve endings, it may act as a neuro-transmitter mediating vasodilatation in the uterus.

Radioimmunoassay of vasoactive intestinal polypeptide

A sensitive radioimmunoassay for plasma vasoactive intestinal polypeptide (VIP) has been developed based on preparations of fully immunoreactive 125I-labeled VIP and hightiter specific antiserum as well as elimination of plasma interference substance(s). Fully immunoreactive 125I-labeled VIP (specific activity = 520 μCi/nmol) was prepared by lactoperoxidase iodination and purified by gel filtration followed by chromatography on an O-(carboxymethyl) (CM)-Sephadex C-25 column. Specific anti-VIP serum produced from New Zealand white rabbits had a titer of 1:500,000 and the following binding parameters: effective affinity constant ( K eff), 2.9 × 10 11 m −1; heterogeneity index (α), 0.57; average affinity constant ( K 0), 2.4 × 10 10 m −1. Interfering substance(s) in plasma samples was proved to be present by direct radioimmunoassay and eliminated by an XAD-2 resin adsorption technique, leading to a minimal overall sensitivity of 0.48 p m for plasma samples. The average plasma VIP concentration of 78 normal fasting human subjects was 5.7 ± 3.4 (SD) p m, and that of 5 patients with watery diarrhea syndrome was 359 ± 93 p m, which reduced gradually to the normal basal value after clinical treatment.

Nervous release of vasoactive intestinal polypeptide in the gastrointestinal tract of cats: possible physiological implications.

1. The release of vasoactive intestinal polypeptide (VIP) into blood from the gastrointestinal tract was studied when eliciting autonomic nervous effects known to be mediated via non-adrenergic, non-cholinergic nerve fibres. All studies were performed on animals given atropine. 2. Electrical stimulation of the low threshold vagal fibres to the stomach did not significantly change gastric volume or VIP concentration in the venous effluent from the stomach. Stimulating the high threshold fibres, on the other hand, produced a gastric relaxation concomitant with a significant increase of venous plasma VIP concentrations. When eliciting a similar vagal relaxation of the stomach by distending a balloon the oesophagus a significant increase of venous plasma VIP concentration was also recorded. 3. Mechanical stimulation of the mucosa of the small bowel increased intestinal blood flow and a significant increase of venous plasma VIP concentration was observed. 4. Stimulation of the pelvic nerves to the colon produced a transient vasodilation and a significant increase of VIP in the venous effluent from the large bowel. A maintained vasodilation in the colon was induced by mechanically stimulating the rectal mucosa. This vascular response was accompanied by a significant raise of venous plasma VIP concentration. 5. The results demonstrate that all the studied nervous effects known to be mediated via non-adrenergic, non-cholinergic nerve fibres were accompanied by significant increases of the VIP concentration in the venous effluent. The possible physiological implications of these findings are discussed and it is proposed that VIP may be a neurotransmitter in the gastrointestinal tract.

Das vasoaktive intestinale Polypeptid beim Verner-Morrison-Syndrom

A 40-year-old man with the Verner-Morrison syndrome (refractory watery diarrhoea and hypokalaemia in islet-cell tumour of the pancreas) had an islet-cell carcinoma of the non-B-cell type with metastases to liver and mesenteric lymph nodes. High concentrations of a vasoactive intestinal polypeptide (VIP) were demonstrated in tumour tissue and plasma by radioimmunological tests. After surgical removal of the tumour the plasma VIP concentration fell to normal. Immunohistochemical tests of the tumour for gastrointestinal hormones demonstrated marked fluorescence only for vaso-active intestinal polypeptide. It is assumed that this polypeptide is largely responsible for the clinical signs. In the described case the severe watery diarrhoea ceased after glucocorticoid administration.