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Congenital constriction band syndrome and transverse deficiency.

To distinguish the clinical features of amputation due to congenital constriction band syndrome from those of transverse deficiency, 42 cases of constriction band syndrome and 27 cases of transverse deficiency were analysed. All the transverse deficiencies were unilateral. Two cases of transverse deficiency were associated with pectoral muscle absence, whereas amputation from constriction band syndrome was often associated with similar anomalies in other parts of the body. The level of amputation of transverse deficiency was more proximal than that of constriction band syndrome. Rudimentary fingers and/or nails were common in transverse deficiency but there were few in constriction band syndrome. Various degrees of bone hypoplasia existed in adjacent fingers or in a proximal part of the affected limb in transverse deficiency, but there were no such findings in constriction band syndrome.

Amniotic Band Syndrome↗

Shroom induces apical constriction and is required for hingepoint formation during neural tube closure.

BACKGROUND: The morphogenetic events of early vertebrate development generally involve the combined actions of several populations of cells, each engaged in a distinct behavior. Neural tube closure, for instance, involves apicobasal cell heightening, apical constriction at hingepoints, convergent extension of the midline, and pushing by the epidermis. Although a large number of genes are known to be required for neural tube closure, in only a very few cases has the affected cell behavior been identified. For example, neural tube closure requires the actin binding protein Shroom, but the cellular basis of Shroom function and how it influences neural tube closure remain to be elucidated. RESULTS: We show here that expression of Shroom is sufficient to organize apical constriction in transcriptionally quiescent, naive epithelial cells but not in non-polarized cells. Shroom-induced apical constriction was associated with enrichment of apically localized actin filaments and required the small GTPase Rap1 but not Rho. Endogenous Xenopus shroom was found to be expressed in cells engaged in apical constriction. Consistent with a role for Shroom in organizing apical constriction, disrupting Shroom function resulted in a specific failure of hingepoint formation, defective neuroepithelial sheet-bending, and failure of neural tube closure. CONCLUSIONS: These data demonstrate that Shroom is an essential regulator of apical constriction during neurulation. The finding that a single protein can initiate this process in epithelial cells establishes that bending of epithelial sheets may be patterned during development by the regulation of expression of single genes.

Actin Cytoskeleton↗

The effect of light intensity and dose of dilute pilocarpine eyedrops on pupillary constriction in healthy subjects.

The aim of this study was to investigate variables that influence the degree of pupillary constriction to dilute pilocarpine eyedrops in healthy control subjects. The pupillary response to 50 microliter of pilocarpine 0.0625% in darkness, dim light, and bright light was measured photographically in 15 healthy adults. Constriction to pilocarpine was greater in darkness and in dim light than in bright light, indicating that the pupillary-light reflex masked the constrictive effect of pilocarpine. In ten other subjects pupillary constriction to 50 microliters of pilocarpine 0.04%, and to 50 and 100 microliters of pilocarpine 0.0625%, was measured on separate occasions. Pupillary constriction increased in proportion to the volume and concentration of pilocarpine. Data for pupillary constriction to 50 microliters of pilocarpine 0.0625% in dim light were determined in all 25 subjects.

Adult↗

The efferent connections of the pupillary constriction area in the rat medial frontal cortex.

This study investigated, in the rat, the efferent projections of the pupillary constriction area, which is located within the medial frontal cortex. In order to identify the location of the pupillary constriction area, in preliminary experiments the medial frontal cortex was microstimulated. Intracortical microstimulation elicited pupillary constriction in a thin strip of cortex near the interhemispheric fissure and bordering the frontal eye field and vibrissae area of the somatomotor cortex. Seven animals received a single iontophoretic injection of Phaseolus vulgaris leucoagglutinin in the pupillary constriction area. In these cases, anterogradely labelled fibres and terminal-like elements were found in both hemispheres. The densest labeling was seen in several areas of the injected hemisphere, where labeled fibers prevailed in the secondary visual cortex. Dense labeled fibers were also found in the retrosplenial and cingulate cortex. In the thalamus, labeled fibers were seen in the intralaminar nuclei and posterior nuclear group. In the midbrain and pons, labeled fibers were located in the anterior pretectal area, superior colliculus and in the dorsolateral portion of the central gray. Contralaterally to the injection site, labeled fibers were distributed in the homotopic region. These findings led us to assume that, in the medial frontal cortex of the rat, besides controlling pupillary constriction, the pupillary constriction area may also be involved in controlling orientation and exploring behavior.

Animals↗

In vivo analysis of adrenergic and serotoninergic constrictions of the rabbit saphenous vein.

We aimed to develop a model to study in vivo the rabbit saphenous vein pharmacology and to investigate constrictions mediated by adrenoceptor and 5-HT receptor subtypes. We used the technique of high precision ultrasonic echo-tracking for direct measurement of saphenous vein diameters in pentobarbital anesthetized rabbits. Saphenous vein constrictions induced in rabbits by the alpha(1)-adrenoceptor agonist L-phenylephrine and the 5-HT(1B) receptor agonist sumatriptan were comparable with those induced in dogs but those induced by the 5-HT(1B) and 5-HT(7) receptor agonist 5-carboxamidotryptamine failed to appear in dogs. Dose-related constrictions of rabbit veins were obtained with L-phenylephrine and the alpha(2)-adrenoceptor agonist dexmedetomidine. Frequency-related constrictions of rabbit veins induced by nerve stimulation were partially inhibited by an alpha(1)-adrenoceptor or a postsynaptic alpha(2)-adrenoceptor antagonist (prazosin and SKF 104,078) but not affected by the pre- and post-synaptic alpha(2)-adrenoceptor antagonists BRL 44408 or rauwolscine. Constrictions of rabbit veins to sumatriptan and 5-CT were inhibited by GR 127935 and those induced by quipazine, a 5-HT(2) receptor agonist were prevented by ritanserin. The initial constrictions induced by 5-CT were followed by dilatations which were inhibited by the 5-HT(7) receptor antagonist mesulergine. These data indicate that rabbit saphenous veins, in vivo and at rest, respond to activation of 5-HT(1B) and 5-HT(2) receptors, alpha(1)- and alpha(2)-adrenoceptors and nerve stimulation; the dilator effect mediated by 5-HT(7) receptor activation was also detected. The data validate a new animal model to study superficial vein reactivity and its pharmacological sensitivity.

Adrenergic Agents↗

The hemodynamics of vacuum constriction erections: assessment by color Doppler ultrasound.

Duplex ultrasound with pulsed Doppler and color flow sonography were used to image the penis and conduct blood flow velocity studies in 5 patients. Cavernous body cross sectional area, cavernous artery diameters and peak systolic velocities were measured in the flaccid shaft, after transient exposure to negative pressure in a vacuum constriction device, and with a vacuum constriction device band applied to the tumescent shaft. We found that exposure to vacuum transiently increased central cavernous arterial blood flow velocities compared to baseline values in all patients. After a trial of a vacuum constriction device and application of the constricting band cavernous body cross sectional areas doubled. Despite increased cavernous arterial diameters in 4 of 5 patients and increased blood flow in all patients after vacuum-induced tumescence alone, we could not visualize arterial inflow in the penile shaft once the constricting band was in place. Color Doppler ultrasound can detect cavernous artery systolic flow as low as 2 to 9 cm. per second. Our data suggest that the erectile state maintained distal to the vacuum constriction device band is low flow and relatively ischemic.

Aged↗

Juxtamedullary afferent and efferent arterioles constrict to renal nerve stimulation.

Sympathetic neural control of afferent and efferent arterioles of inner cortical (juxtamedullary) glomeruli has not been established, in part, because of difficulty accessing these vessels, normally located deep below the kidney surface. In this study we utilized the rat hydronephrotic kidney model to visualize the renal microcirculation and to quantitate the responses of juxtamedullary arterioles to brief (30 sec) renal nerve stimulated (RNS). Juxtamedullary afferent and efferent arterioles constricted in a frequency-dependent fashion to RNS, achieving a maximal constriction of 35% to 8 Hz stimulation. In these same kidneys, outer cortical afferent arterioles also constricted to RNS but outer cortical efferent arterioles did not. Microinjection of norepinephrine (NE) around single outer cortical efferent arterioles (to avoid the constriction of preglomerular vessels) constricted the efferent arterioles. However, the afferent arterioles of the same glomeruli were considerably more responsive to microinjected NE. Thus, the lack of constriction of outer cortical efferent arterioles to RNS may relate, in part, to their low sensitivity to NE, the primary neurotransmitter. These direct observations indicate that the juxtamedullary efferent arterioles are responsive to renal nerve stimulation whereas the outer cortical efferent vessels are not. These results, which should be cautiously extrapolated to normal filtering kidneys, indicate that glomerular hemodynamic changes evoked by the sympathetic nervous system are different for outer cortical and inner cortical glomeruli.

Animals↗

Cellular signalling in arteriolar myogenic constriction: involvement of tyrosine phosphorylation pathways.

1. An increase in transmural pressure in arterioles results in a shortening of vascular smooth muscle cells, with subsequent constriction of the vessel. The mechanisms underlying this myogenic contraction are not fully understood; however, the obligatory role of increases in intracellular [Ca(2+)] and myosin light chain phosphorylation have been demonstrated. 2. The myogenic response shows a relationship with smooth muscle cell membrane potential and influx of extracellular Ca(2+) through voltage-operated Ca(2+) channels (VOCC). Mechanically sensitive channels and possibly release of Ca(2+) from intracellular stores may play a role. However, there are other components of myogenic contraction that cannot be explained by a Ca(2+)-MLCK mechanism, for example the initial sensing of alterations in transmural pressure, whether sustained myogenic constriction involves myofilament Ca(2+) sensitization or remodelling of the vessel wall in response to a maintained increase in transmural pressure. 3. In an attempt to investigate these areas, recent studies have examined a role for tyrosine phosphorylation pathways in pressure-induced contraction of arterioles. In rat pressurized cremaster arterioles, tyrosine kinase inhibitors dilated vessels showing spontaneous myogenic tone and tyrosine phosphatase inhibitors caused vasoconstriction. However, pressure-induced myogenic constriction of vessels persisted in the presence of these agents. Biochemical studies revealed that phosphotyrosine formed at a relatively slow rate (significant after 5 min, with maximal increase after approximately 15 min) in response to increased vessel transmural pressure, in contrast with myosin light chain phosphorylation or the time-course of myogenic constriction itself (maximum within 1 min). 4. Taken together, these observations support the idea of a role for tyrosine phosphorylation pathways in longer-term responses to increased transmural pressure rather than acute myogenic constriction. Phosphotyrosine formation was also more closely correlated to vessel wall tension (pressure x diameter) than the diameter of the arterioles alone. The identity of the tyrosine-phosphorylated proteins requires further investigation; however, there is some evidence supporting roles for cSrc-type tyrosine kinases and p44 mitogen-activated protein kinase. The longer-term responses of blood vessels to increased transmural pressure that may involve tyrosine phosphorylation pathways include maintenance of myogenic constriction and vessel wall remodelling.

Animals↗

Effects of stretch or distention on phenylephrine-induced constriction of human coronary artery bypass grafts.

OBJECTIVE: To determine the effects of grafting saphenous veins into the arterial circulation and to compare the responsiveness of saphenous veins and mammary arteries to vasoconstrictors (phenylephrine or potassium) and a vasodilator (the calcium antagonist isradipine). DESIGN: Prospective, controlled, in vitro study. SETTING: Laboratory facility in a university teaching hospital. PARTICIPANTS: Small excess segments of internal mammary arteries or saphenous veins obtained from patients undergoing coronary artery bypass graft surgery. INTERVENTIONS: Vessel segments were cut into rings to measure isometric tension development in isolated tissue chambers. The law of LaPlace for a cylinder was applied to determine tensions in vitro corresponding with arterial or venous tensions in vivo or distending pressures ex vivo. MEASUREMENTS AND MAIN RESULTS: Stretching saphenous vein rings from venous to arterial tensions reduced maximal phenylephrine-induced constriction but did not alter their dose response to phenylephrine, potassium, or isradipine. At arterial tensions, potassium, but not phenylephrine, was more potent in constricting mammary artery than saphenous vein; isradipine was more potent as a vasodilator of potassium-constricted mammary artery than saphenous vein. Maximal phenylephrine-induced or potassium-induced constriction was no different for either vessel at arterial tensions; however, prior distention of veins to tensions corresponding with pressures of 200 or 300 mmHg significantly (p < 0.01, Dunnett's test) reduced subsequent constriction. CONCLUSION: Phenylephrine may be more likely to constrict native internal mammary arteries than distended autogenous saphenous vein grafts in vivo because high-pressure distention of veins markedly inhibits their vasoreactivity.

Coronary Artery Bypass↗

Reversibility of Nuclear and 3D Genomic Changes in Non-Cancerous Fibroblasts After Constricted Migration.

Metastatic cancer cells and healthy fibroblasts must traverse constrictive spaces to reach secondary sites. After passing through multiple constrictions, cancer cells often experience stable changes to their nucleus morphology, 3D genome structure, and migratory phenotype. Here, we investigate whether fibroblasts (BJ-5ta), which are non-cancerous and have an inherent ability to migrate to fulfill roles in wound repair, likewise experience nuclear and 3D genomic changes with constricted migration. We find that BJ-5ta cells only slightly increase their migratory capacity after sequential constricted migrations but do experience nuclear deformations and 3D genome alterations at the compartment level after constricted migration. Transient compartment shifts spatially rearranged genes associated with preparation for and response to migration. Unlike the stable changes associated with long term phenotype changes in cancer cells, however, the nucleus deformations recovered back to unmigrated levels following proliferation and cell movement. Some compartment changes persist and might influence responses to future stimuli, but most 3D genome changes revert to the unmigrated state after cell proliferation. Our study shows that non-cancerous migratory cells are not necessarily less susceptible to nucleus and 3D genome alterations caused by constricted migration, but do recover from such alterations more readily than cancer cells. [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text].

Journal Article↗

Cadmium-induced arteriolar constriction in skeletal muscle microcirculation.

Cadmium, an environmental pollutant, is known to induce hypertension in animal models, in part via an increase in peripheral vascular resistance. Since prior studies have investigated the vascular effects of cadmium using large, nonresistance arteries, we directly assessed cadmium's action on resistance size arterioles in skeletal muscle using the intact rat cremaster muscle preparation. Cadmium evoked a concentration-dependent constriction of the large arterioles (120 to 50 microns in diameter) but elicited no change in the diameter of smaller arterioles (30 to 15 microns). Blockade of alpha-adrenergic receptors did not diminish the constrictor response of the larger arterioles to cadmium, but bathing the cremaster muscles with a solution containing low calcium attenuated the arteriolar constriction to cadmium. Calcium repletion caused the arterioles to constrict further. These observations provide the first direct evidence that cadmium constricts resistance arterioles in skeletal muscle. The cadmium constriction: (1) is selective for the large arterioles, (2) is not mediated by alpha-adrenergic receptors, and (3) is influenced by the extracellular level of calcium. We conclude that arteriolar constriction in skeletal muscle tissue may play a role in the hypertensive actions of cadmium.

Animals↗

An in vitro comparison of the sealing ability of three endodontic sealers used in canals with iatrogenic enlargement of the apical constriction.

In cases of disrupted apical constriction effort is made to create an apical stop and subsequently instrument and obturate the canal up to this point. The aim of this study was to in vitro evaluate the sealing ability of three root canal sealers used with the lateral compaction technique in teeth with enlarged constriction. Thirty-six single rooted premolars with straight canals were instrumented up to the apical constriction using a step-back technique. The constriction was enlarged and root canal instrumentation 1.5 mm short of the original working length was performed, to create a new apical stop. Teeth were obturated using lateral compaction technique with either Topseal, Roth 811, or Apexit. Teeth were subjected to area-metric analysis of dye penetration in transverse root sections, up to the most coronal extend of the dye. Sections were studied under the stereomicroscope, digital images were processed and leakage area was estimated. Statistical analysis was performed using Student's t test and Wilcoxon matched-pairs signed-rank test. No gutta-percha was extruded into the space between the apical constriction and the new iatrogenically created constriction. Topseal showed statistical significant less leakage. No significant difference was found between Apexit and Roth 811 (t = 0.99; p = 0.75).

Bicuspid↗

Mechanosensitive cation channels mediate afferent arteriolar myogenic constriction in the isolated rat kidney.

1. In order to assess ionic mechanisms mediating renal afferent arteriolar myogenic constriction, experiments were performed using isolated perfused hydronephrotic rat kidneys. 2. Increasing pressure progressively constricted the afferent arteriole (-0.26 +/- 0.02% mmHg-1, n = 21, r = 0.97). Gadolinium (10 microM), a mechanosensitive cation channel blocker, abolished this myogenic constriction. However, high potassium media (30 mM) constricted the afferent arteriole in the presence of gadolinium. 3. Lowering extracellular sodium concentration gradually attenuated afferent arteriolar myogenic constriction. In the perfusate containing 50 mM sodium, the myogenic response was arrested. 4. Afferent arteriolar myogenic constriction was prevented in calcium-free perfusate or by the L-type calcium channel blocker diltiazem (10 microM). 5. Our present findings provide evidence that increasing pressure gates mechanosensitive cation channels on the afferent arteriole, thereby eliciting membrane depolarization and activating voltage-dependent calcium channels.

Animals↗

Noradrenaline-induced constriction of large and small coronary arteries in the anaesthetized dog.

1. In the anaesthetized dog external diameter of the left circumflex coronary artery and blood flow through that artery were measured to allow the effect of noradrenaline to be compared in large arteries and resistance vessels. 2. The injection of noradrenaline (0.5 micrograms kg-1) into the coronary artery, after bilateral vagotomy and antagonism of beta-adrenoreceptors, decreased large coronary artery diameter and coronary blood flow. Calculation of resistance in the large coronary artery and in the total left circumflex coronary vascular bed revealed that noradrenaline induced increases of 66% and 89% respectively. 3. Intra-coronary (i.c.) injection of the alpha 1-adrenoreceptor agonist phenylephrine (0.5-2 micrograms kg-1) decreased large coronary artery diameter and coronary blood flow. The alpha 2-adrenoreceptor agonist B-HT 920 (0.5-2 micrograms kg-1 i.c.) decreased coronary blood flow but did not significantly affect large coronary artery diameter. 4. Antagonism of alpha 1-adrenoreceptors with prazosin (10 micrograms kg-1 i.c.) abolished the noradrenaline-induced constriction of the large coronary artery but only partially attenuated the decrease in blood flow. The alpha 2-adrenoreceptor antagonist idazoxan (50 micrograms kg-1 i.c.) partially attenuated the noradrenaline-induced decrease in coronary blood flow but did not affect the large artery constriction. 5. It is concluded that noradrenaline constricts both large and small coronary arteries. Noradrenaline-induced constriction of the resistance vessels is more powerful than in the large artery. The constriction of large arteries in response to noradrenaline is mediated by alpha 1-adrenoreceptors. Postjunctional alpha 1- and alpha 2-adrenoreceptors are both involved in the constriction of the resistance vessels.

Adrenergic alpha-Agonists↗

Blockade of noradrenaline-induced constrictions by yohimbine and prazosin differs between consecutive segments of cutaneous arteries in guinea-pig ears.

1. The study has examined the receptors mediating constriction produced by brief local application of noradrenaline (NA) to cutaneous arteries and arterioles in the ear vasculature of anaesthetized guinea-pigs. The innervation of the corresponding vascular segments has been examined immunohistochemically at the conclusion of the pharmacological experiments. 2. Small arteries of branch order 4 (4 degrees, 40-110 microns internal diameter) were more sensitive to the vasoconstrictor action of NA than were more proximal arteries of branch order 3 (3 degrees, 60-150 microns internal diameter), or more distal arteries and arterioles of branch orders 5 to 7 (5 degrees-7 degrees, 18-85 microns internal diameter). This higher sensitivity of 4 degrees arteries was maintained after blockade of neuronal uptake with desipramine (1 microM), and after blockade of beta-adrenoceptors with propranolol (1 microM). 3. NA-induced vasoconstrictions of distal arterioles (5 degrees-7 degrees) were abolished or greatly reduced by yohimbine (1 microM). The blockade by yohimbine decreased progressively with increasing vessel diameter of proximal arteries, while the blockade by prazosin (1 microM) increased progressively in arteries > 40 microns diameter. 4. In 3 degrees and 4 degrees arteries, a substantial component (approximately 50%) of NA-induced vasoconstrictions remained after combined treatment with yohimbine and prazosin, in the presence or absence of desipramine. These constrictions were not further reduced by benextramine (1-10 microM), but were abolished by dihydroergotamine (1-10 microM). Constrictions induced by ATP (0.1-1 mM) were not affected by dihydroergotamine. 5. 5-Hydroxytryptamine (3-100 microM) had a variable effect on 3 degree and 4 degree arteries including: concentration dependent constrictions (n = 3); small constrictions at some concentrations, and dilatations or no change in diameter at other concentrations (n = 6); concentration-dependent dilatations only (n = 3). The 5-HT2 receptor antagonist, ketanserin (0.1-0.3 micro M), did not affect NA-induced constrictions.6. In 16 arterial segments ranging from 3 degree arteries to 60 arterioles, there was a significant correlation between the presence of neuropeptide Y-immunoreactive (NPY-IR) sympathetic axons and the degree of blockade of NA-induced constrictions by yohimbine, prazosin and dihydroergotamine.7. These results demonstrate marked differences in the postsynaptic adrenoceptors mediating vasoconstriction to a bolus of NA applied briefly to the adventitial surface of different segments of the cutaneous vasculature of the guinea-pig ear. Furthermore, the presence or absence of adrenoceptors sensitive to blockade by yohimbine or prazosin is related to the proportion of sympathetic axons innervating each vascular segment which contain NPY-IR.

Animals↗

Studies of the renal component of the hypertension in rats with aortic constriction. Role of angiotensin II.

The object of this study was to investigate the renal component of hypertension in aortic constriction. In 40-day-old Sprague-Dawley rats the aorta were constricted either proximal (PAC) or distal (DAC) to the renal arteries. The rats were examined 3 weeks later together with control rats. The arterial pressure proximal to the constriction was elevated in the PAC group but not in the DAC group. In PAC rats the arterial pressure was also elevated distal to the constriction. There was a significant pressure gradient across the constriction in both PAC and DAC rats. The PAC rats had a significant decrease of renal blood flow, a significant increase in renal vascular resistance and a numerical but not significant decrease of glomerular filtration rate. Serum levels of angiotensin II were not significantly different in PAC and control rats. The pressor effect of a bolus dose of angiotensin II was significantly increased in PAC rats. Captopril, a converting enzyme inhibitor, decreased the arterial pressures and renal vascular resistance in PAC rats. The pressure elevating effects of angiotensin II and pressure lowering effect of captopril were more pronounced distal than proximal to the constriction. We conclude that the kidneys play a major role in the development of hypertension in PAC, and that the local effect of angiotensin II on the renal vascular bed is an important contributor to the renal component of the hypertension.

Angiotensin II↗

Constriction and septation during cell division in caulobacters.

Morphogenesis of the division site in caulobacters had been described as constrictive in Caulobacter spp. and septate in Asticcacaulis excentricus. However, subsequent studies of other gram-negative genera had implied that constrictive division was an artefact resulting from inadequate preservation of septa; exploration of alternatives to osmium fixation, particularly with aldehydes, was recommended. In this study, the appearance of sectioned division sites was reinvestigated in caulobacter cells prepared by 20 different procedures varying with respect to fixation agents, media, schedules, and temperatures, to dehydrating agents, and to embedding resins. Three types of division site morphogenesis were observed: constriction in C. bacteroides and C. crescentus, partial septation in C. leidyi, and complete, undivided septation in A. excentricus and A. biprosthecum. The anatomy of the division site depended on the bacterial strain, not on the method of preparation of the cells for sectioning. These studies confirm the earlier observations on osmium-fixed caulobacter cells and lead to the general conclusion that gram-negative bacteria with tapered poles probably divide by constriction, whereas septation results in blunt cell poles. A pattern of spiral, rather than circular, insertion of new envelope subunits at the cell equator is proposed as a basic developmental difference between constrictive and septate fission in gram-negative bacteria. Since caulobacter prosthecae can develop as extensions of tapered poles formed by constriction, whereas subpolar or lateral prosthecae occur in species with blunt poles resulting from septation, the site of formation of a thick septum appears unsuitable as a site of subsequent envelope outgrowth.

Bacteria↗

Arterial constriction, ischemia-reperfusion, and leukocyte adherence in acute pancreatitis.

We investigated microcirculatory changes in sodium taurocholate (ST)-induced pancreatitis. Groups of rats received as tracer either fluorescein isothiocyanate-dextran or acridine orange intravenously. The microcirculation of the exposed pancreas was observed by use of a video camera attached to an epi-illumination microscope. Vessel diameters and plaques of adherent leukocytes were measured with a digital image-analyzing system. In contrast to 0.4 ml of saline, intraductal infusion of ST (4%, 0.4 ml) induced a constriction of interlobular pancreatic arteries of 79 +/- 2% (P < 0.01) within 2 min. This constriction could not be antagonized by the leukotriene antagonist CGP-35949B. The radical scavengers superoxide dismutase (SOD) and N-(2-mercaptopropionyl)glycine (MPG) prevented the arterial constriction. Constriction of pancreatic arteries was accompanied by a decrease of erythrocyte velocity in the pancreatic capillaries. Flux in the head of the pancreas measured by laser-Doppler velocimetry decreased from 300 +/- 69 to 74 +/- 23 perfusion units (P < 0.01) after 446 +/- 159 s. Subsequently an increase of perfusion values was observed indicating reperfusion phenomena. ST induced leukocyte adherence to the walls of interlobular veins forming plaques constituting 39% of the observed venular cross section within 6 min. The leukotriene antagonist, SOD, or MPG prevented leukocyte adherence. Arterial constriction followed by ischemia-reperfusion and leukocyte adherence to venular endothelium during the reperfusion period represented the sequence of microcirculatory changes in ST-induced pancreatitis. The radical scavengers SOD and MPG prevented arterial constriction and leukocyte adherence to venular endothelium, indicating the involvement of free radicals in the pathogenesis of ST-induced pancreatitis in the rat.

Acute Disease↗