Intravenous Infusion Of Histamine Research Articles

Source of dopamine in gastric juice and luminal dopamine-induced duodenal bicarbonate secretion via apical dopamine D2 receptors.

Dopamine protects the duodenal mucosa. Here we have investigated the source of dopamine in gastric juice and the mechanism underlying the effects of luminal dopamine on duodenal bicarbonate secretion (DBS) in rodents. Immunofluorescence, UPLC-MS/MS, gastric incubation and perfusion were used to detect gastric-derived dopamine. Immunofluorescence and RT-PCR were used to examine the expression of dopamine receptors in the duodenal mucosa. Real-time pH titration and pHi measurement were performed to investigate DBS. H+ -K+ -ATPase was co-localized with tyrosine hydroxylase and dopamine transporters in gastric parietal cells. Dopamine was increased in in vivo gastric perfusate after intravenous infusion of histamine and in gastric mucosa incubated, in vitro, with bethanechol chloride or tyrosine. D2 receptors were the most abundant dopamine receptors in rat duodenum, mainly distributed on the apical membrane of epithelial cells. Luminal dopamine increased DBS in a concentration-dependent manner, an effect mimicked by a D2 receptor agonist quinpirole and inhibited by the D2 receptor antagonist L741,626, in vivo D2 receptor siRNA and in D2 receptor -/- mice. Dopamine and quinpirole raised the duodenal enterocyte pHi . Quinpirole-evoked DBS and PI3K/Akt activity were inhibited by calcium chelator BAPTA-AM or in D2 receptor-/- mice. Dopamine in the gastric juice is derived from parietal cells and is secreted along with gastric acid. On arrival in the duodenal lumen, dopamine increased DBS via an apical D2 receptor- and calcium-dependent pathway. Our data provide novel insights into the protective effects of dopamine on the duodenal mucosa.

An investigation of the mechanisms responsible for a reduction in capillary filtration coefficient in the innervated cat jejunum on intravenous infusion of histamine.

An investigation of the mechanisms responsible for a reduction in capillary filtration coefficient in the innervated cat jejunum on intravenous infusion of histamine.

PERIPHERAL DOPAMINE D2‐LIKE RECEPTORS HAVE A REGULATORY EFFECT ON CARBACHOL‐, HISTAMINE‐ AND PENTAGASTRIN‐STIMULATED GASTRIC ACID SECRETION

It has been documented that dopamine, an important regulator of gastric function in the brain-gut axis, has an inhibitory effect on the gastric acid secretion. It has also been suggested that dopamine D1, D2 and D5 receptor proteins are present in the gastrointestinal tract from the stomach through to the distal colon. Therefore, we hypothesized that peripheral D2 receptors may be involved in the control of stimulated gastric acid secretion. To address this question, we examined the effect of quinpirole, a selective D2 receptor-like agonist, and domperidone, a peripheral D2 receptor antagonist, on rat gastric acid secretion. Quinpirole (0.0001-0.5 mg/kg, i.p.) was administered simultaneously with intravenous infusions of histamine, pentagastrin, and carbachol. In some experiments, domperidone (3 and 7 mg/kg) was administered 30 min before quinpirole injection. We found that intraperitoneal injection of quinpirole (0.0001-0.5 mg/kg) suppressed stimulated gastric acid secretion induced by histamine (0.08 mg/100 g per h), pentagastrin (1 microg/100 g per h) and carbachol (4 microg/100 g per h) in a dose-dependent manner. This inhibitory effect of quinpirole persisted until the end of the experiments (90-120 min) and was completely suppressed by domperidone (7 mg/kg). In conclusion, the results of the present study suggest that peripheral D2-like receptors have an inhibitory effect on histaminergic-, pentagastrin- and cholinergic-stimulated gastric acid secretion. This inhibitory effect may be mediated by enteric dopaminergic neurons and/or non-neuronal membranes.

Maximal gastric secretion in smokers and non-smokers with duodenal ulcer.

Sex, stature, age and smoking habits were investigated as possible determinants of maximal gastric secretion in pre-operative patients with duodenal ulcer. Stimulation was by an intravenous infusion of histamine (130 nmol kg-1 h-1) in 201 patients. Men were found to secrete significantly more than women, and smokers secreted significantly more than non-smokers. By multiple regression analysis, height and the total number of cigarettes smoked were found to be significant positive, and age significant negative factors in the magnitude of maximal gastric secretion. Upon standardization for these factors, the differences between the sexes and the smoking groups disappeared. It is suggested that, at least in men, chronic smoking increases maximal gastric secretion, and therefore could have a role in the aetiology of duodenal ulcer.

Dual action of prostaglandin E2 on gastric acid secretion through different EP-receptor subtypes in the rat

We examined the role of prostaglandin E (EP) receptor subtypes in the regulation of gastric acid secretion in the rat. Under urethane anesthesia, the stomach was superfused with saline, and the acid secretion was determined at pH 7.0 by adding 50 mM NaOH. The acid secretion was stimulated by intravenous infusion of histamine or pentagastrin. Various EP agonists were administered intravenously, whereas EP antagonists were given subcutaneously 30 min or intravenously 10 min before EP agonists. PGE(2) suppressed the acid secretion stimulated by either histamine or pentagastrin in a dose-dependent manner. The acid inhibitory effect of PGE(2) was mimicked by sulprostone (EP(1)/EP(3) agonist) but not butaprost (EP(2) agonist) or AE1-329 (EP(4) agonist). The inhibitory effect of sulprostone, which was not affected by ONO-8711 (EP(1) antagonist), was more potent against pentagastrin- (50% inhibition dose: 3.6 mug/kg) than histamine-stimulated acid secretion (50% inhibition dose: 18.0 mug/kg). Pentagastrin increased the luminal release of histamine, and this response was also inhibited by sulprostone. On the other hand, AE1-329 (EP(4) agonist) stimulated the acid secretion in vagotomized animals with a significant increase in luminal histamine. This effect of AE1-329 was totally abolished by cimetidine as well as AE3-208 (EP(4) antagonist). These results suggest that PGE(2) has a dual effect on acid secretion: inhibition mediated by EP(3) receptors and stimulation through EP(4) receptors. The former effect may be brought about by suppression at both parietal and enterochromaffin-like cells, whereas the latter effect may be mediated by histamine released from enterochromaffin-like cells.

Endothelial permeability for macromolecules. Mechanistic aspects of pathophysiological modulation.

The endothelium separates blood from tissue and actively regulates the exchange between these compartments. Throughout the body, this one-cell-thick lining of blood vessels extends over several thousand square meters. It harbors many receptors and functions that actively regulate the extravasation of nutrients, solutes, hormones, macromolecules, and leukocytes. If the barrier function of the endothelium does not perform appropriately, leakage of macromolecules occurs, causing edema formation and exposure of the interstitium to high concentrations of plasma constituents. In severe cases of vascular leakage, platelets will adhere to the exposed subendothelium and red blood cells may even accumulate in the interstitium. Vascular leakage may be desirable for recruiting plasma proteins, such as complement factors during infection, but it can become life-threatening, particularly when it occurs in the lungs or pericardium or when it causes hypovolemic shock. Furthermore, frequent or prolonged leakage may impair proper functioning of the affected tissue. In recent years, considerable progress has been made in understanding the molecular processes that contribute to the regulation of endothelial permeability. With the exception of the liver, adrenal, and bone marrow sinusoids, in which the endothelium has rather large pores, the endothelium constitutes a selective barrier between blood and tissue. In principle, this barrier consists of the EC monolayer and its matrix. Macromolecules can cross the endothelial barrier in three ways: (1) between the cells, through cell junctions (paracellular); (2) through the EC, via pores (diaphragms or fused vesicles); and (3) transcellularly, via shuttling vesicles and specific receptors. It is generally believed that the charge and compactness of the endothelial matrix (both glycocalyx and basal membrane) contribute additionally to the selectivity of the endothelial barrier toward molecules of different size and charge. Electron microscopic evidence strongly suggests that in tissue capillaries, hormones and macromolecules are shuttled across the endothelial barrier via vesicles, in …

Effects of Maturation on Changes in Lung Mechanics During Continuous Intravenous Infusion of Histamine in Piglets. 1796

Background. Increases in lung resistance (RL) due to i.v. histamine bolus are reported to become more pronounced with postnatal maturation (Dreshaj et al; J. Appl. Physiol. 81(4): 1785-1791, 1996). Objective. To determine if postnatal development affects the changes in RL and lung elastance (EL =1/compliance) during constant infusion of histamine. Methods. We continuously measured airway opening pressure (Pao), flow and esophageal pressure (Pes) during 30-minute intravenous infusions of histamine in seven tracheostomized, anesthetized, paralyzed and mechanically ventilated (constant tidal volume) piglets [3 newborn (4-6 days, 2.5-3.0 Kg) and 4 weaned (8 weeks, 12.3-18 Kg)]. Measurements were repeated at two concentrations (0.5 and 5.0 μg/Kg/min). RL and EL were determined by multiple linear regression; i.e., Pao(t)-Pes(t)=RL·flow(t) + EL·volume(t). Results. For both groups, RL and EL increased with histamine in a dose dependent fashion. The increases in EL were comparable regardless of dose. Changes in RL were similar at the lower histamine dose (figure). At the higher dose, the increases in RL were similar during early infusion ( 10 min) in older piglets. Conclusion. Differences in the response to histamine, in older versus newborn piglets, were only evident as a sharper rise in RL during the latter part of the higher dose infusion. Such age dependence of RL is consistent with histamine bolus data. We speculate that this phenomenon may be related to increased central airway involvement in the response as opposed to a predominantly peripheral effect because: 1) the sharp rise in RL did not coincide with a similar increase in EL, and 2) rise in RL only occurs late, when accumulation of histamine may have led to bolus-like conditions. Supported in part by an equipment grant from Novametrix Medical Systems Inc.

Differential responses of global airway, terminal airway, and tissue impedances to histamine.

The forced oscillation and alveolar capsule techniques were applied to determine the input impedance of the lungs and the airway transfer impedances between 0.2 and 20 Hz in six open-chest dogs in the control state, during intravenous infusion of histamine at seven rates between 0.25 and 16 micrograms.kg-1.min-1, and after the infusion. In each condition, the input impedances seen from the alveolar capsules, i.e., terminal airway impedance (Zaw,ter), were measured by imposing 2- to 200-Hz oscillations from the capsules (B. L. K. Davey and J. H. T. Bates. Respir. Physiol. 91:165-182, 1993). Airway resistance (Raw) and inertance and tissue damping and elastance were derived from the lung impedance data. For all dogs, histamine progressively increased Raw and the real part of airway transfer impedance (airway transfer resistance), reaching, at 16 micrograms.kg-1.min-1, 241 +/- 109 (SD) and 370 +/- 186%, respectively, of the control value but caused greater, although locally highly variable, increases (769 +/- 716% of the control value) in the real part of Zaw,ter extrapolated to zero frequency (R0). With increasing doses of histamine, the changes in R0 always preceded those in Raw and airway transfer resistance implying that bronchoconstriction developed first in the lung periphery. It is therefore concluded that the measurement of Zaw,ter offers a sensitive method for the detection of early nonuniform responses to bronchoconstrictor stimuli that are not yet reflected by the values of the overall Raw. In one-half of the cases, significant increases in tissue damping and elastance occurred before any change in R0; this suggests that the mechanisms of airway and parenchymal constrictions may be unrelated.

Antisecretory Effect of Leminoprazole on Histamine-Stimulated Gastric Acid Secretion in Dogs: Potent Local Effect

Leminoprazole, an acid pump inhibitor, significantly reduces basal and stimulated gastric acid secretion in rats when administered via the systemic or local route. Our aim here was to characterize the antisecretory effect of leminoprazole on gastric acid secretion in conscious dogs. Gastric acid secretion by dogs with a vagally denervated Heidenhain pouch was stimulated by intravenous histamine infusion. Leminoprazole or omeprazole (as a reference drug) was administered either intravenously or locally into the pouch before or after histamine infusion. A bolus intravenous administration of leminoprazole and omeprazole, respectively, significantly and dose-relatedly inhibited the stimulated gastric acid secretion for >26 hr. Local application of leminoprazole, but not omeprazole, significantly inhibited the acid secretion when applied for 15 to 30 min. The duration of the local antisecretory effect observed after 30 min application was around 8–10 hr. The acid-degraded products of leminoprazole had no effect when applied to the pouch. The blood concentration of leminoprazole was very low at 1 hr after local application. These results indicate that leminoprazole suppresses the secretory function of the parietal cells of dogs, via both the intravenous and local routes. It remains unknown whether or not locally applied leminoprazole produced the acid inhibition by inhibiting the acid pump.

The Role of Nitric Oxide in Migraine Pain

In recent years, an increasing volume of evidence has suggested that the small messenger molecule nitric oxide (NO) plays a pivotal role in migraine pain. This evidence is mainly based on experimental studies using 2 different human headache models — intravenous infusion of nitroglycerin (glyceryl trinitrate) [a donor of NO] and intravenous infusion of histamine (which probably activates endothelial NO formation). These models offer unique possibilities for the study of NO mechanisms in migraine. Data suggest that NO is involved in the aetiology of migraine, a finding that may open up a number of possibilities for future drug treatments of the disorder.

Contribution of viscoelastic stress to the rate-dependence of pulmonary dynamic elastance

To further characterize the contribution of the stresses accumulated during inflation in viscoelastic elements of the lungs to the rate-dependence of pulmonary dynamic elastance, we analyzed the changes in the pressures measured at the airway opening and in subpleural air spaces during airway occlusions performed at constant inflation rates of 5, 10, 20 and 40 ml/(kg sec) in 13 anesthetized piglets (mean age = 7 days). The analyses was repeated after saline lavage of the lungs and during intravenous infusion of histamine in 7 and 4 of the piglets, respectively. Viscoelastic stresses dissipated as stress relaxation were solely responsible for the differences between dynamic and static elastance before and after lung lavage and for more than 40% of this difference during histamine infusion (the remainder probably being caused by ventilation inequalities). The viscoelastic contribution to dynamic elastance increased by more than two-fold after lung lavage and was independent of inflation rate and only minimally dependent upon inflation volume. Our results demonstrate that viscoelastic stresses are primarily responsible for the dynamic stiffening of piglet lungs at low rates of inflation. They also support the notion that viscoelastic and elastic stresses are couple as the lungs inflate.

Secretagogue-specific effects of interleukin-1 on gastric acid secretion

Interleukin-1 beta (IL-1 beta) has recently been shown to reduce the severity of experimental gastroduodenal damage and to inhibit acid secretion in the pylorus-ligated rat. In the present study, the effects of IL-1 beta on pentagastrin-stimulated acid secretion were compared with those of two other cytokines, namely IL-1 alpha and tumor necrosis factor (TNF) alpha. Also, the effects of IL-1 beta on gastric acid secretion stimulated by bethanechol or histamine were assessed. Anesthetized rats were pretreated intravenously with one of the cytokines, at doses in the 0.1-5 micrograms/kg range, 30 min before starting an intravenous infusion of pentagastrin. TNF alpha failed to significantly affect acid secretion, whereas IL-1 alpha and IL-1 beta exhibited significant inhibitory effects. For example, at a dose of 5 micrograms/kg, IL-1 alpha and IL-1 beta reduced acid secretion by 33 and 80%, respectively. The inhibitory effects of IL-1 beta on acid secretion could be completely inhibited by preincubation with an antibody directed against IL-1 beta but not by pretreatment with indomethacin (5 mg/kg sc) or by bilateral vagotomy. If acid secretion was stimulated by intravenous infusions of histamine or bethanechol, neither IL-1 beta nor TNF alpha produced significant inhibitory effects. Inhibition of acid secretion by IL-1 was also observed when the IL-1 was administered subsequent to stimulation by pentagastrin administration. These results demonstrate that IL-1 beta is an extremely potent inhibitor of acid secretion stimulated by pentagastrin but not that stimulated by histamine or bethanechol, through a mechanism that is at least in part independent of the vagus nerve and of prostaglandin synthesis. IL-1 alpha is less potent as an inhibitor of gastric acid secretion, whereas TNF appears to be inactive. Because pentagastrin-stimulated acid secretion could be completely inhibited by a histamine H2-receptor antagonist (cimetidine) and because IL-1 had no effect on histamine-stimulated acid secretion, it is possible that IL-1 exerts its antisecretory actions by inhibiting pentagastrin-stimulated histamine release.

Plasma histamine and clinical tolerance to infused histamine in normal, atopic and urticarial subjects

Five subjects with a recent history of urticaria (U), five atopic (A) subjects and a non-atopic (NA) control group were given intravenous infusions of histamine starting at 0.05 micrograms/kg/min, increasing by 0.05 micrograms/kg/min every 30 minutes to a maximum of 0.35 micrograms/kg/min. Plasma histamine levels were monitored every 15 minutes. The infusion was stopped when an objective clinical endpoint was reached, involving either evidence of peripheral vasodilatation (rise of skin temperature by at least 1 degree C) or a 20% fall of peak expiratory flow rate. There were no significant differences in resting plasma histamine in the three groups. Those with urticaria reached the clinical endpoint at a lower infusion rate than non-atopic subjects (U 0.22 +/- 0.02 micrograms/kg/min; A 0.26 +/- 0.02 micrograms/kg/min; NA 0.32 +/- 0.2 micrograms/kg/min. p less than 0.008) they also received a lower total histamine dose (U 1.12 +/- 0.33 mg; A 1.42 +/- 0.38 mg, NA 2.2 +/- 0.51 mg, p less than 0.008). Atopic subjects with a history of asthma, eczema or rhinitis also tolerated histamine poorly, some subjects reaching a clinical endpoint while the plasma histamine level was still relatively low (U 1.52 +/- 0.4 ng/ml, A 0.85 +/- 0.19 ng/ml, NA 1.4 +/- 0.44 ng/ml, p = 0.05). After the histamine infusion was stopped, the fall in the blood level of histamine was slower in urticarial subjects than in the other two groups, with a half-life of 6.2 +/- 1.3 min (A 3.0 +/- 1.2 min, NA 4.0 +/- 0.7 min, p less than 0.02). There were thus differences in the metabolism of histamine in our non-atopic urticarial subjects and increased histamine sensitivity in atopic subjects which require further study.

Biostatistical modeling of the effect of intravenous histamine-infusion on the rat gastric acid secretion

In this study, a variety of linear and nonlinear biostatistical models of regression were tested to evaluate the histamine-induced gastric acid secretion using the lumen-perfusion model in the rat. Among the linear, parabolic, and polynomial models tested, 3rd- and 4th-order polynomial models of regression exerted best correlations between the time and histamine-induced gastric acid secretion. In order to avoid undulatory behaviors in the regression curves, we conducted the polynomial regression analysis up to 5th order.

Role of acetylcholine, histamine and gastrin in the acid response to intracisternal injection of TRH analog, RX 77368, in the rat

The role of gastrin, acetylcholine and histamine in the acid response to central vagal activation induced by intracisternal injection of the stable analog, RX 77368, was further investigated in urethane-anesthetized rats with gastric fistula. The gastrin monoclonal antibody 28-2 injected intravenously, at a dose previously shown to prevent gastrin-induced stimulation of acid secretion, did not alter the peak acid response to intracisternal injection of RX 77368 (15 ng). The TRH analog (30 ng) injected into the cisterna magna increased levels of histamine measured in the hepatic portal blood. Cimetidine administered at a dose which completely blocked the stimulation of gastric acid secretion produced by intravenous infusion of histamine, inhibited by 62% the stimulatory effect of intracisternal RX 77368 (30 ng). The M1 muscarinic antagonist, pirenzepine, completely prevented the acid secretion induced by intracisternal RX 77368 (30 ng). These results indicate that the acid response to central vagal activation by the TRH analog in rats involved M1 muscarinic receptors along with histamine release acting on H 2 histaminergic receptors whereas gastrin does not appear to play an important role.

Action of histamine on the rapidly adapting airway receptors in the dog.

The effects of histamine on the activity of rapidly adapting receptors (RAR) of the airways were investigated in anesthetized dogs. With bolus injections given into the right atrium, the threshold dose of histamine required for the excitation of RAR (n = 7) was 0.82 microgram/kg (+1.33/-0.51, geometric mean). With increasing doses of histamine, a dose-response relationship was seen in the activity of RAR. Obstruction of the lymphatic drainage from the lungs reduced the threshold dose to histamine (i.e., shifted the dose-response curve to the left significantly). This change in the dose-response relationship was not accompanied by a corresponding change in the relationship of histamine dose to airway pressures recorded before and after lymphatic obstruction. Against a background of pulmonary venous congestion produced by partial obstruction of the mitral valve, subthreshold doses of histamine stimulated the RAR (n = 4). The excitatory effect of histamine on RAR was found to be abolished by the administration of the H1 receptor antagonist diphenhydramine but not by the H2 receptor antagonist cimetidine. Intravenous infusion of histamine (0.4 microgram.kg-1.min-1) for a period of 10 min increased the RAR activity (n = 6) significantly without producing detectable changes in airway mechanics. The results indicate that contraction of the smooth muscle of the airways may not be a prerequisite for the excitation of RAR, especially at low doses. It is suggested that some of the effects of histamine on RAR are mediated by a local expansion of the extravascular fluid caused by an increase in the permeability of the bronchial vasculature.

Anti-acid secretion activity of drugs cimetidine, ranitidine, tiotidine D 15,144 in dogs fixed with gastric fistulae

1. 1. Acid secretion for each dog has reached a near maximum (100%) at the 6th samples, 90 min after the intravenous infusion of histamine (10 μghr −1, or approximately equal to 0.3 mghr −1). 2. 2. 0.5 mgkg −1 Cimetidine had produced a mean inhibition of 47% on the stomach. 3. 3. 0.1 mgkg −1 Ranitidine (D 14,951) could only inhibit a maximum of 28%, and the secretion had return to normal in just 30 min. 4. 4. 0.025 mgkg −1 Tiotidine (D 15,104) had inhibited 53% acid secretion within 15 min of exposure. Recovery was quite similar to that of Cimetidine, at 150 min. 5. 5. At a dosage one fifth of Cimetidine (0.1 mgkg −1) D 15,144 had depressed 35% of acid secretion at the first 15 min. The inhibition is gradually increased to about 43% (at 30 min), and was maintained for the next 105 min.

Histamine and Nt-methylhistamine in the circulation during intravenous infusion of histamine in normal volunteers.

Plasma levels of histamine and Nt-methylhistamine were measured simultaneously by high performance liquid chromatography during the intravenous infusion of histamine acid phosphate in six normal volunteers. Progressive, dose-related increases in plasma histamine were noted, reaching a maximum value of 3.1 +/- 0.14 ng ml-1 corresponding to a maximum infusion rate of 180 ng kg-1 min-1 (means +/- SEM). Increases in plasma histamine were accompanied by a significant dose-related fall in mean diastolic blood pressure (baseline 74.0 +/- 4.4 mm Hg falling to 60.0 +/- 3.3 mm Hg at maximum infusion rate, p less than 0.001) and an increase in pulse rate (baseline 76.3 +/- 2.8 beats min-1 rising to 89.24 beats min-1 at maximum infusion rate, p less than 0.05). All subjects exhibited facial flushing, the threshold plasma histamine level for this effect being 1.3 +/- 0.15 ng ml-1 corresponding to an infusion rate of 60 ng kg-1 min-1. Elevation of plasma Nt-methylhistamine was seen in only one subject, who exhibited a level of 0.5 ng ml-1 at the highest infusion rate. These results suggest that measurements of plasma Nt-methylhistamine are unlikely to provide a useful index of histamine release into the circulation.

Importance of pepsin and stomach distension in morphological alterations of stress-induced gastric lesions in pylorus-ligated rats.

Pylorus ligation changed the morphology and location of gastric lesions induced by water-immersion stress (WI stress) in rats; linear lesions in the corpus mucosa disappeared, and punctate lesions appeared in both the corpus and antrum, in association with the loss of H+ and the gain of Na+ in the gastric contents. Oral administration of antipeptic drugs such as amylopectin sulfate and sulfated glyptide or porcine pepsin significantly prevented or aggravated the lesions, respectively, although another type of elongated lesion appeared in response to high doses of antipeptic drugs. These antipeptic drugs or exogenous pepsin significantly reduced or increased pepsin activity, respectively, without effect on the acid output. Similar punctate lesions were produced in the atropinized rats (10 mg/kg) by instillation of acid solution (100 mM HCl plus 54 mM NaCl) with pepsin into the pylorus-ligated stomach and subjecting to WI stress. On the other hand, when the gastric contents were drained through a fistula to prevent accumulation of gastric juice in the pylorus-ligated stomach, WI stress again induced linear lesions only in the corpus mucosa. Acid hypersecretion in these rats induced by intravenous infusion of histamine, tetragastrin, or carbachol significantly aggravated the severity of lesions but did not change their morphology. These results suggest that pepsin in the presence of acid is prerequisite for development of gastric lesions in pylorus-ligated rats induced by WI stress. The morphological alterations may be accounted for by the distensions of the stomach due to accumulation of gastric juice in the lumen caused by pylorus ligation, but not due to acid hypersecretion.

Investigation of adrenomedullary function in atopic dermatitis.

Adrenomedullary function in patients with atopic dermatitis was assessed by measurement of plasma levels of catecholamines (adrenalin and noradrenalin) and cyclic AMP in response to the stimuli of standing after lying supine, and a 5-min infusion of histamine in the standing position (i.e. histamine plus standing). Plasma clearance of adrenalin was examined by measurement of plasma catecholamine and cyclic AMP levels following a 15-min intravenous infusion of adrenalin in the supine position. Resting plasma levels of adrenalin, cyclic AMP and noradrenalin were not statistically different in atopic patients and normal controls. Standing or intravenous infusion of histamine in the standing position caused a rise in plasma catecholamine levels. Plasma adrenalin, cyclic AMP and noradrenalin levels in response to these stimuli and the rate of clearance of exogenous adrenalin from the plasma were not significantly different in patients with atopic dermatitis and in normal subjects.