scholarly journals Expression of urocortin in rat lung and its effect on pulmonary vascular permeability

2006 ◽  
Vol 189 (1) ◽  
pp. 167-178 ◽  
Author(s):  
Yuqing Wu ◽  
Yinyan Xu ◽  
Hong Zhou ◽  
Jin Tao ◽  
Shengnan Li
Keyword(s):  
Receptor Antagonist ◽  
Vascular Permeability ◽  
Alveolar Epithelium ◽  
Bronchial Epithelium ◽  
Rat Lung ◽  
Pulmonary Vascular Permeability ◽  
Peripheral Tissues ◽  
The Central Nervous System ◽  
Hematoxylin And Eosin ◽  
Lung Vascular Permeability

Urocortin (UCN), a newly identified, 40-amino-acid, corticotropin-releasing hormone (CRH) structurally related peptide, has been demonstrated to be expressed in the central nervous system and many peripheral tissues of rats and man. This study aimed to investigate the expression profile of UCN in rat lung and the effect of UCN on lung vascular permeability. The expression of UCN mRNA was detected by reverse transcriptase PCR (RT–PCR). UCN peptide was measured by immunohistochemistry and Western blot analysis. We found that both UCN mRNA and peptide were obviously expressed in rat lung. Immunohistochemistry results showed that UCN peptide is mainly expressed in bronchial epithelium mucosa and alveolar epithelium. We also found that rats receiving inhalation aerosol of UCN had a significant elevation of lung vascular permeability compared with rats receiving vehicle and ovalbumin (OVA) by the Evans blue (EB) technique. UCN aerosol inhalation resulted in obvious pulmonary congestion and edema observed under light microscope by hematoxylin and eosin (HE) staining. The nonselective peptide CRH receptor antagonist astressin markedly reduced lung vascular permeability triggered by UCN. Enhanced pulmonary vascular permeability induced by UCN was markedly inhibited by pretreatment with the mast-cell stabilizer cromolyn and histamine-1 (H1) receptor antagonist azelastine respectively, but not by the leukotriene receptor antagonist montelukast. In summary, in the present study, we demonstrated for the first time that UCN is expressed in rat lung and contributes to an increase in lung vascular permeability through activation of CRH receptors. Mast cells and histamine may be involved in this effect of UCN. Peripherally produced UCN in lung may act as an autocrine and paracrine proinflammatory factor.

Cholecystokinin octapeptide analogues suppress food intake via central CCK-A receptors in mice

1993 ◽  
Vol 265 (3) ◽  
pp. R481-R486 ◽  
Author(s):  
Y. Hirosue ◽  
A. Inui ◽  
A. Teranishi ◽  
M. Miura ◽  
M. Nakajima ◽  
...  
Keyword(s):  
Food Intake ◽  
Receptor Antagonist ◽  
Rank Order ◽  
Peripheral Circulation ◽  
Inhibitory Effect ◽  
Peripheral Tissues ◽  
Cholecystokinin Octapeptide ◽  
The Central Nervous System ◽  
The Difference ◽  
The Brain

To examine the mechanism of the satiety-producing effect of cholecystokinin (CCK) in the central nervous system, we compared the potency of intraperitoneally (ip) or intracerebroventricularly (icv) administered CCK-8 and its analogues on food intake in fasted mice. The icv administration of a small dose of CCK-8 (0.03 nmol/brain) or of Suc-(Thr28, Leu29, MePhe33)-CCK-7 (0.001 nmol/brain) suppressed food intake for 20 min, whereas CCK-8 (1 nmol/kg, which is equivalent to 0.03 nmol/brain) or Suc-(Thr28, Leu29, MePhe33)-CCK-7 (1 nmol/kg) had satiety effect after ip administration. Dose-response studies indicated the following rank order of potency: Suc-CCK-7 > or = Suc-(Thr28, Leu29, MePhe33)-CCK-7 > or = CCK-8 > or = (Nle28,31)-CCK-8 >> desulfated CCK-8 = CCK-4 = 0 in the case of ip administration and Suc-(Thr28, Leu29, MePhe33)-CCK-7 >> Suc-CCK-7 > or = CCK-8 > or = (Nle28,31)-CCK-8 >> desulfated CCK-8 = CCK-4 = 0 in the case of icv administration. The selective CCK-A receptor antagonist MK-329 reversed the inhibitory effect of the centrally as well as peripherally administered CCK-8, or of Suc-(Thr28, Leu29, MePhe33)-CCK-7, whereas the selective CCK-B receptor antagonist L-365260 did not. The icv administered CCK-8 did not appear in the peripheral circulation. These findings suggest the participation of CCK-A receptors in the brain in mediating the satiety effect of CCK and the difference in CCK-A receptors in the brain and peripheral tissues.

scholarly journals Bacillus anthracis lethal toxin, but not edema toxin, increases pulmonary artery pressure and permeability in isolated perfused rat lungs

2019 ◽  
Vol 316 (5) ◽  
pp. H1076-H1090 ◽  
Author(s):  
Xizhong Cui ◽  
Wanying Xu ◽  
Pranita Neupane ◽  
Andie Weiser-Schlesinger ◽  
Ray Weng ◽  
...  
Keyword(s):  
Pulmonary Artery ◽  
Bacillus Anthracis ◽  
Vascular Permeability ◽  
Pulmonary Artery Pressure ◽  
Lethal Toxin ◽  
Rat Lung ◽  
Fluid Accumulation ◽  
Pulmonary Vascular Permeability ◽  
Artery Pressure ◽  
Edema Toxin

Although lethal toxin (LT) and edema toxin (ET) contribute to lethality during Bacillus anthracis infection, whether they increase vascular permeability and the extravascular fluid accumulation characterizing this infection is unclear. We employed an isolated perfused Sprague-Dawley rat lung model to investigate LT and ET effects on pulmonary vascular permeability. Lungs ( n ≥ 6 per experimental group) were isolated, ventilated, suspended from a force transducer, and perfused. Lung weight and pulmonary artery (Ppa) and left atrial pressures were measured over 4 h, after which pulmonary capillary filtration coefficients (Kf.c) and lung wet-to-dry weight ratios (W/D) were determined. When compared with controls, LT increased Ppa over 4 h and Kf.c and W/D at 4 h ( P < 0.0001). ET decreased Ppa in a significant trend ( P = 0.09) but did not significantly alter Kf.c or W/D ( P ≥ 0.29). Edema toxin actually blocked LT increases in Ppa but not LT increases in Kf.c and W/D. When Ppa was maintained at control levels, LT still increased Kf.c and W/D ( P ≤ 0.004). Increasing the dose of each toxin five times significantly increased and a toxin-directed monoclonal antibody decreased the effects of each toxin ( P ≤ 0.05). Two rho-kinase inhibitors (GSK269962 and Y27632) decreased LT increases in Ppa ( P ≤ 0.02) but actually increased Kf.c and W/D in LT and control lungs ( P ≤ 0.05). A vascular endothelial growth factor receptor inhibitor (ZM323881) had no significant effect ( P ≥ 0.63) with LT. Thus, LT but not ET can increase pulmonary vascular permeability independent of increased Ppa and could contribute to pulmonary fluid accumulation during anthrax infection. However, pulmonary vascular dilation with ET could disrupt protective hypoxic vasoconstriction. NEW & NOTEWORTHY The most important findings from the present study are that Bacillus anthracis lethal toxin increases pulmonary artery pressure and pulmonary permeability independently in the isolated rat lung, whereas edema toxin decreases the former and does not increase permeability. Each effect could be a basis for organ dysfunction in patients with this lethal infection. These findings further support the need for adjunctive therapies that limit the effects of both toxins during infection.

Effect of ischemia reperfusion or hypoxia reoxygenation on lung vascular permeability and resistance

1990 ◽  
Vol 69 (2) ◽  
pp. 597-603 ◽  
Author(s):  
R. C. Allison ◽  
J. Kyle ◽  
W. K. Adkins ◽  
V. R. Prasad ◽  
J. M. McCord ◽  
...  
Keyword(s):  
Blood Flow ◽  
Reperfusion Injury ◽  
Vascular Permeability ◽  
Vascular Resistance ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Pulmonary Vascular Permeability ◽  
Permeability Changes ◽  
Lung Vascular Permeability ◽  
Hypoxia Reoxygenation

The effect of ischemia reperfusion or hypoxia reoxygenation on pulmonary vascular permeability and resistance was studied in 25 isolated blood-perfused dog lungs. Vascular permeability, assessed by determining filtration coefficient (Kf), and vascular resistances were measured at the beginning and end of the experiment. Ischemia reperfusion was produced by occluding blood flow to the lung for 3 h and reperfusing for 1 h, whereas hypoxia reoxygenation was obtained by ventilating the lung with 95% N2-5% CO2 for 3 h and then ventilating with 95% O2-5% CO2 for 1 h with no interruption of perfusion. There was a significant increase in Kf in both ischemia reperfusion and hypoxia reoxygenation groups (51 and 85%, respectively), and total vascular resistance increased greatly in both groups (386 and 532%, respectively). Two additional groups were also studied in which the ischemia reperfusion or hypoxia reoxygenation lungs were pretreated with allopurinol (20 micrograms/ml). The Kf did not significantly increase in either the allopurinol ischemia reperfusion or the allopurinol hypoxia reoxygenation groups (22 and 6%, respectively). However, total vascular resistance significantly increased in both groups (239 and 224%, respectively). Although vascular permeability is modestly increased by both ischemia reperfusion and hypoxia reoxygenation, the predominant change in these conditions is the increased vascular resistance, which predominantly affects the postcapillary resistance and would result in a greater tendency for edema to develop in these slightly damaged lungs. Allopurinol, which inhibits xanthine oxidase, attenuated the permeability changes in both groups and may be useful in preventing ischemia reperfusion injury in certain conditions.

Leukocyte repletion reverses protective effect of neutropenia in thrombin-induced increase in lung vascular permeability

1990 ◽  
Vol 259 (1) ◽  
pp. H149-H155 ◽  
Author(s):  
S. K. Lo ◽  
R. R. Garcia-Szabo ◽  
A. B. Malik
Keyword(s):  
Vascular Permeability ◽  
Lymph Flow ◽  
Control Group ◽  
Base Line ◽  
Pulmonary Vascular Permeability ◽  
Protein Clearance ◽  
Pulmonary Hemodynamic ◽  
Lung Lymph ◽  
Lung Vascular Permeability

We examined the role of leukocytes in the pathogenesis of lung vascular injury induced by thrombin in awake sheep prepared with the lung lymph fistulas. Thrombin (80 U/kg) infusion in control sheep (n = 6) increased pulmonary arterial pressure (Ppa) twofold and pulmonary vascular resistance (PVR) three-fold for the 5-h experimental period. Thrombin also increased pulmonary vascular permeability to protein as assessed by decrease in the reflection coefficient (sigma) from 0.70 +/- 0.03 to 0.61 +/- 0.01. Thrombin caused similar initial pulmonary hemodynamic changes in sheep rendered neutropenic (n = 7; 2% neutrophil count of controls) by treatment with hydroxyurea; however, both Ppa and PVR returned toward base-line values within 120 min postthrombin challenge. The increases in pulmonary lymph flow and transvascular protein clearance also recovered rapidly beginning at 60 min after challenge with thrombin in neutropenic sheep. Neutropenia prevented the increase in lung vascular permeability as the sigma value of 0.71 +/- 0.02 was similar to the control value. Leukocytes isolated from control donor sheep were infused intra-arterially into recipient neutropenic sheep (n = 4) to assess the effects of neutrophil repletion on the pulmonary vascular responses. Thrombin (80 U/kg) challenge infused at 1-3 h after infusion of leukocytes increased lung lymph flow twofold and transvascular protein clearance fourfold and produced increases in Ppa and PVR comparable with the control group. The increases in these parameters were sustained for the 5-h experiment duration. The data indicate the essential pathogenetic role of neutrophils in mediating the thrombin-induced increase in lung vascular permeability.

scholarly journals Effect of PAF on rat lung vascular permeability: role of platelets and polymorphonuclear leucocytes

1994 ◽  
Vol 111 (4) ◽  
pp. 1111-1116 ◽  
Author(s):  
Martin G. Sirois ◽  
Wothan Tavares Lima ◽  
Artur José de Brum Fernandes ◽  
Richard J. Johnson ◽  
Gérard E. Plante ◽  
...  
Keyword(s):  
Vascular Permeability ◽  
Polymorphonuclear Leucocytes ◽  
Rat Lung ◽  
Lung Vascular Permeability

Hypoxia increases pulmonary vascular permeability in isolated rat lung

1994 ◽  
Vol 1 ◽  
pp. 412 ◽  
Author(s):  
S. Ueda ◽  
T. Tanita ◽  
S. Ono ◽  
M. Noda ◽  
T. Tabata ◽  
...  
Keyword(s):  
Vascular Permeability ◽  
Rat Lung ◽  
Pulmonary Vascular Permeability ◽  
Isolated Rat Lung ◽  
Isolated Rat

Role of circulating blood components and thromboxane in anaphylactic vasoconstriction in isolated canine lungs

1997 ◽  
Vol 83 (5) ◽  
pp. 1508-1516 ◽  
Author(s):  
Takashige Miyahara ◽  
Toshishige Shibamoto ◽  
Hong-Gang Wang ◽  
Shozo Koyama
Keyword(s):  
Receptor Antagonist ◽  
Vascular Permeability ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Autologous Blood ◽  
Lower Lobe ◽  
Blood Perfusion ◽  
Blood Components ◽  
Pulmonary Vascular Permeability

Miyahara, Takashige, Toshishige Shibamoto, Hong-Gang Wang, and Shozo Koyama. Role of circulating blood components and thromboxane in anaphylactic vasoconstriction in isolated canine lungs. J. Appl. Physiol. 83(5): 1508–1516, 1997.—We determined the roles of circulating blood components and chemical mediators in anaphylactic vasoconstriction and microvascular permeability during Ascaris suum antigen-induced anaphylaxis in isolated canine lungs. Either the right or left lower lobe served as the control lung, which was perfused with autologous blood, and the contralateral lobe from the same dog was examined for the effect of albumin Krebs-Henseleit solution (Krebs) or of blockers of various vasoconstrictors with blood perfusion. Pulmonary vasoconstriction occurred after injection of the antigen (15 mg) in both the blood- and Krebs-perfused lungs. However, the percent change of peak pulmonary vascular resistance in the Krebs-perfused lungs tended to be greater than that in the blood-perfused lungs (689.9 ± 289.3 and 389.3 ± 171.9%, respectively). This increased peak pulmonary vascular resistance was attenuated similarly by pretreatment with indomethacin (1.1 × 10−4 M; cyclooxygenase inhibitor), AA-2414 (10−5 M; thromboxane-receptor antagonist), or a combination of TCV-309 (10−5 M; platelet-activating factor-receptor antagonist), diphenhydramine (1.7 × 10−4 M, histamine H1-receptor antagonist), and indomethacin but not by pretreatment with TCV-309 or diphenhydramine alone. The filtration coefficient, an index of vascular permeability, did not change significantly at 15 or 60 min after the antigen in all groups. These findings suggest that anaphylactic vasoconstriction in the isolated canine lung is independent of circulating blood components. Thromboxane is the major mediator for the anaphylactic vasoconstriction. Anaphylaxis does not increase pulmonary vascular permeability in isolated canine lungs.

scholarly journals Endothelial EphA receptor stimulation increases lung vascular permeability

2008 ◽  
Vol 295 (3) ◽  
pp. L431-L439 ◽  
Author(s):  
Jacqueline Larson ◽  
Stacey Schomberg ◽  
William Schroeder ◽  
Todd C. Carpenter
Keyword(s):  
Vascular Permeability ◽  
Tyrosine Kinases ◽  
Vascular Endothelial Cells ◽  
Normal Lung ◽  
Pulmonary Vascular Permeability ◽  
Histological Evidence ◽  
Lung Vascular Permeability ◽  
Stimulation Of

Mediators of angiogenesis such as VEGFs and angiopoietins may regulate pulmonary vascular permeability under normal and pathological conditions. Ephrin family receptor tyrosine kinases are expressed in the vasculature and also regulate angiogenesis under some circumstances, but whether they also modulate lung vascular permeability is unknown. We hypothesized that stimulation of lung endothelial EphA receptors with ephrin-a1 ligand would alter pulmonary vascular permeability and tested this idea in vivo and in vitro. We found that ephrin-a1 ligand and EphA2 receptors are expressed in distal normal lung vasculature and that their expression is increased in injured lung, suggesting a link to mechanisms of increased permeability. Intravenous injection of ephrin-a1 caused a large increase in the leakage of labeled albumin into the lungs of rats within 30 min (293 ± 27 vs. 150 ± 6 ng/mg dry lung, P < 0.01), along with histological evidence of the formation of endothelial disruptions. In cultured lung vascular endothelial cells, stimulation with ephrin-a1 increased monolayer permeability by 44% ( P < 0.01), a permeability change similar to that seen with VEGF stimulation of the same cells. Ephrin-a1 stimulation in vivo and in vitro was associated with histological evidence for disruptions of tight and adherens junctions. These observations describe a novel role for ephrin-a1 and EphA receptors in the regulation of vascular permeability in the lung.

Isolated premature menarche in two siblings with Neurofibromatosis type 1

2020 ◽  
Vol 33 (6) ◽  
pp. 813-816
Author(s):  
James Blackburn ◽  
Mohammed Didi ◽  
Shivaram Avula ◽  
Senthil Senniappan
Keyword(s):  
Neurofibromatosis Type 1 ◽  
Pubertal Timing ◽  
Genetic Disorder ◽  
Pubertal Development ◽  
Neurofibromatosis Type ◽  
Malignant Tumours ◽  
Peripheral Tissues ◽  
Paediatric Endocrinology ◽  
The Central Nervous System

AbstractObjectivesNeurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder, caused by mutation in NF1. The condition is typified by the development of benign and malignant tumours in both the central nervous system and peripheral tissues. Isolated menarche is a sub-classification of incomplete isosexual precocious puberty typified by menarche in girls with no other features of pubertal development. The effects of NF1 on pubertal timing are poorly understood, we report two siblings with NF1 and apparent abnormal pubertal development.Case PresentationTwo siblings were referred to the tertiary paediatric endocrinology clinic at 6 and 7 years of age with recurrent, cyclical vaginal bleeding. There was a strong family history of NF1, the mother of the siblings and two brothers were also diagnosed at a young age. On examination both patients were prepubertal at presentation. Both siblings underwent a gonadotrophin releasing hormone test, which revealed a follicle-stimulating hormone dominant (prepubertal) response. The features were suggestive of isolated premature menarche as no other cause was identified. The elder sibling established menarche and developed signs of consonant pubertal development at 12 years of age. The younger sibling remains under regular follow-up.ConclusionsNF1 has previously been associated with alterations in pubertal timing. We report, for the first time, two siblings with NF1 who presented with isolated menarche.

Sign in / Sign up

Export Citation Format

Share Document