Neural control of vascular permeability: interactions between primary afferents, mast cells, and sympathetic efferents

1989 ◽  
Vol 62 (1) ◽  
pp. 48-58 ◽  
Author(s):  
T. J. Coderre ◽  
A. I. Basbaum ◽  
J. D. Levine
Keyword(s):  
Blood Pressure ◽  
Mast Cells ◽  
Vascular Permeability ◽  
Neural Control ◽  
Primary Afferents ◽  
Sympathetic Chain ◽  
Blue Dye ◽  
Base Line ◽  
Plasma Extravasation ◽  
Sympathetic Efferents

1. This study addressed the contribution of primary afferents, mast cells, and sympathetic efferents to the control of vascular permeability in synovial joints. Extravasation of Evans blue dye into the synovial space was measured by perfusion of the knee joint in the adult rat. Plasma extravasation (PE) was evoked by pharmacologic activation of either unmyelinated primary afferents, mast cells, or sympathetic postganglionic nerve (SPGN) terminals with acute injection of either capsaicin, compound 48/80, or 6-hydroxydopamine (6-OHDA), respectively. In otherwise untreated control rats, acute infusion of capsaicin or compound 48/80 produced a brief increase in vascular permeability; infusion of 6-OHDA produced a larger and more prolonged increase. 2. To evaluate the contribution of an interaction of different cellular elements in the joint to PE, we repeated these experiments in rats pretreated with capsaicin, compound 48/80, or 6-OHDA; administered quercetin; or surgically sympathectomized by excision of the lumbar sympathetic chain. Eliminating unmyelinated afferent nerve terminals by neonatal treatment with capsaicin only reduced the increase in PE produced by acute infusion of capsaicin. Degranulating mast cells by pretreatment with compound 48/80, or preventing the degranulation of mast cells by treatment with quercetin, reduced the increase in PE evoked by infusion of either capsaicin or compound 48/80. Finally, sympathectomy, produced by excision of the lumbar sympathetic chain or by pretreatment with 6-OHDA, significantly reduced PE elicited by acute infusion of capsaicin, compound 48/80, or 6-OHDA. 3. Neither infusing substances normally localized to sympathetic efferents nor inducing changes in blood pressure could mimic the profound increase in PE evoked by activation of sympathetic postganglionic neurons with acute infusion of 6-OHDA. Thus norepinephrine produced a significant decrease in PE, adenosine triphosphate produced only a brief increase, neuropeptide Y had no effect, and manipulating blood pressure (either up or down) had no effect on either base-line or 6-OHDA-induced PE. 4. Indomethacin treatment significantly reduced the increase in PE produced by 6-OHDA. This effect of indomethacin was reversed by the addition of prostaglandin E2 (PGE2) to the 6-OHDA in the perfusion fluid. This finding implicates prostaglandins (i.e., cyclooxygenase products of arachidonic acid metabolism) in SPGN-dependent generation of PE.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of platelet-activating factor on airway vascular permeability: possible mechanisms

1987 ◽  
Vol 63 (2) ◽  
pp. 479-484 ◽  
Author(s):  
T. W. Evans ◽  
K. F. Chung ◽  
D. F. Rogers ◽  
P. J. Barnes
Keyword(s):  
Vascular Permeability ◽  
Evans Blue ◽  
Platelet Activating Factor ◽  
Blue Dye ◽  
Base Line ◽  
Plasma Extravasation ◽  
Dependent Manner ◽  
Lipoxygenase Inhibitor ◽  
Dose Dependent ◽  
Evans Blue Extravasation

We studied the effects of the potent inflammatory mediator, platelet-activating factor (PAF), on vascular permeability in airways (and other tissues) of guinea pigs by measuring extravasation of circulating Evans blue dye. PAF caused a dose-dependent increase in vascular permeability. At 1 ng/kg iv, PAF caused an increase in Evans blue extravasation of 220% (P less than 0.05) in the trachea, with the greatest effect at a dose of 100 ng/kg (858%; P less than 0.01). Histamine (150 micrograms/kg iv) caused a 320% increase over base line in the trachea and 200% in main bronchi; this effect was equivalent to that induced by 10 ng/kg PAF in the trachea and 1 ng/kg in main bronchi. The duration of effect of PAF was greatest in main bronchi (less than 10 min). Platelet depletion with a cytotoxic antibody, or the cyclooxygenase inhibitor, indomethacin, or the cyclooxygenase-lipoxygenase inhibitor, BW 7556, did not affect the vascular permeability response to PAF. The PAF-receptor antagonist, BN 52063, inhibited Evans blue extravasation in the airways in a dose-dependent manner, with complete inhibition at 5 mg/kg. Thus PAF-induced airway vascular leakage is mediated by specific receptors but not by products of arachidonic acid metabolism or by platelets. Increased airway microvascular leakage induced by PAF may lead to plasma extravasation and airway edema, factors that may contribute to the airway narrowing and hyperresponsiveness induced by PAF.

Plasma extravasation induced by neurokinins in conscious rats: receptor characterization with agonists and antagonists

1993 ◽  
Vol 71 (3-4) ◽  
pp. 217-221 ◽  
Author(s):  
Mauro Nicolau ◽  
Martin G. Sirois ◽  
Michel Bui ◽  
Gérard E. Plante ◽  
Pierre Sirois ◽  
...  
Keyword(s):  
Substance P ◽  
Urinary Bladder ◽  
Vascular Permeability ◽  
Blue Dye ◽  
Receptor Subtype ◽  
Plasma Extravasation ◽  
Functional Sites ◽  
Conscious Rats ◽  
Selective Antagonists ◽  
Selective Agonists

The purpose of the present experiments was to study the effects of various neurokinin related peptides, such as substance P, [βAla8]NKA(4–10), and [MePhe7]NKB, which are selective for NK-1, NK-2, and NK-3 functional sites, respectively, to induce plasma extravasation in rats and the effectiveness of RP 67580 and CP-96,345 (two nonpeptide NK-1 receptor selective antagonists) and SR 48968 (a nonpeptide NK-2 receptor selective antagonist) to prevent such an effect. Bolus intravenous injection of substance P (1.0 nmol/kg) into conscious rats induced extravasation of Evans blue dye (EB), a selective marker of albumin vascular permeability, in the duodenum, the stomach, the pancreas, and the urinary bladder by 50, 40, 58, and 312%, respectively; a slight increment occurred also in the ileum and the kidney but was not significant. [βAla8]NKA(4–10) (1.0 nmol/kg) increased EB extravasation in the stomach and the urinary bladder by 52 and 99%, respectively, while [MePhe7]NKB (1.0 nmol/kg) did the same in the stomach, the ileum, and the urinary bladder by 58, 50, and 79%. Pretreatment with RP 67580 (250 nmol/kg) blocked the albumin extravasation mediated by substance P in the duodenum, the pancreas, and the urinary bladder by 100, 100, and 78%, respectively. CP-96,345 (250 nmol/kg) also inhibited EB extravasation mediated by substance P in the duodenum and the pancreas by 100 and 100%, respectively, but was ineffective in the urinary bladder. Neither RP 67580 nor CP-96,345 prevented the substance P mediated extravasation in the stomach. RP 67580 and CP-96,345 did not antagonize the effects of NK-2 and NK-3 selective agonists. SR 48968 (500 nmol/kg) was inactive against substance P as well as against the NK-2 or NK-3 selective agonists. RP 67580 (250 nmol/kg), CP-96,345 (250 nmol/kg), and SR 48968 (500 nmol/kg) per se did not induce any plasma extravasation, except in the urinary bladder, where CP-96,345 and SR 48968 increased EB concentrations in the tissue. These results suggest that the effects of neurokinins on vascular permeability vary from one tissue to another. The blockade of substance P by the NK-1 receptor selective antagonists, RP 67580 and CP-96,345, suggests that NK-1 receptors play an important role in the plasma extravasation induced by substance P. However, the effects of NK-2 and NK-3 receptor selective agonists appear to be independent of activation of NK-1 receptors since they are not blocked by RP 67580 or CP-96,345. Furthermore, because the effect of [βAla8]NKA(4–10), the NK-2 selective agonist, was not abolished by SR 48968, it is suggested that it might be mediated by the NK-2 receptor subtype NK-2B, which is less sensitive to SR 48968 than is NK-2A. The contribution of NK-3 receptors to plasma extravasation could not be adequately demonstrated in the present study because NK-3 antagonists sufficiently active in vivo are not available.Key words: neurokinins, RP 67580, CP-96,345, SR 48968, vascular permeability.

scholarly journals Angiopoietin-2 is released during anaphylactic hypotension in anesthetized and unanesthetized rats

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242026
Author(s):  
Tao Zhang ◽  
Toshishige Shibamoto ◽  
Mamoru Tanida ◽  
Makoto Taniguchi ◽  
Yuhichi Kuda ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Skeletal Muscle ◽  
Acute Lung Injury ◽  
Growth Factor ◽  
Vascular Permeability ◽  
Plasma Levels ◽  
Blue Dye ◽  
Arterial Blood ◽  
Tnf Α ◽  
Angiopoietin 2

Angiopoietin (Angpt)-2, a permeability-increasing growth factor, is involved in vascular leakage of sepsis and acute lung injury, and could be released from endothelium in response to anaphylaxis-related secretagogues such as histamine and leukotrienes, or cytokines. However, roles of Angpt-2 in the hyperpermeability during systemic anaphylaxis are not known. Thus, we determined plasma levels of Angpt-2 and cytokines and vascular permeability during anaphylactic hypotension in unanesthetized rats. Anaphylaxis was induced by an intravenous injection of ovalbumin antigen. Mean arterial blood pressure (MBP) was measured, and hematocrit (Hct) and plasma levels of Angpt-2 and cytokines were assessed for 24 h after antigen injection. Separately, vascular permeability was measured in various organs using the Evans blue dye method, and Angpt-2 mRNA expression in liver was measured. After antigen injection, MBP decreased to the nadir at 6 min, and returned to baseline at 45 min, and Hct peaked at 20 min and thereafter progressively declined, suggesting that vascular leak and hypotension occurred within 20 min. Plasma Angpt-2 levels began to increase significantly at 1 h after antigen, reaching the peak 2.7-fold baseline at 6 h with a return to baseline at 24 h. Detected cytokines of IL-1α, IL-1β, IL-6, IL-10, and TNF-α peaked 1 or 2 h after antigen. Angpt-2 mRNA increased at 2 h and showed an increasing tendency at 6 h. Vascular permeability in bronchus, trachea, intestines, mesentery and skeletal muscle was increased at 10 min but not at 6 h after antigen. In addition, we confirmed using anesthetized rat anaphylaxis models that plasma Angpt-2 levels increased at 1 h after antigen. In conclusion, plasma Angpt-2 is elevated presumably due to increased cytokines and enhanced gene transcription during anaphylaxis in anesthetized and unanesthetized rats.

Histamine release and circulating cells after antigen inhalation in allergic dogs

1987 ◽  
Vol 62 (1) ◽  
pp. 253-258 ◽  
Author(s):  
K. F. Chung ◽  
M. L. Osborne ◽  
R. J. Corrales ◽  
T. W. Evans ◽  
L. McCabe ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Mast Cells ◽  
Time Course ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Antigen Challenge ◽  
Base Line ◽  
Plasma Histamine ◽  
Pulmonary Resistance ◽  
Circulating Cells

Histamine can be recovered from the blood of ragweed-sensitized dogs after aerosol antigen challenge, although its source is unknown. Neutrophils and eosinophils have been recovered from bronchoalveolar lavage fluid (BALF) obtained under identical conditions. We investigated the time course of changes in histamine levels in plasma and BALF taken from ragweed-sensitized dogs after aerosol challenge. Changes in the numbers of circulating neutrophils, eosinophils, lymphocytes, monocytes, and platelets were also studied. After 3 min, total pulmonary resistance (RL) was maximally increased and systolic blood pressure was maximally decreased. Histamine levels in plasma and BALF were increased and circulating eosinophils and neutrophils were decreased. After 15 min, platelet numbers were reduced. By 90 min, changes in RL, blood pressure, plasma and BALF histamine concentrations, and circulating neutrophils and eosinophils had returned to base-line values, but platelet numbers remained significantly decreased. Sham challenge caused no significant changes in any of these variables. Intravenous administration of histamine in doses large enough to attain plasma levels comparable with those achieved after aerosol antigen challenge resulted in no concomitant rise in BALF histamine levels. We conclude that antigen challenge in sensitized dogs causes increases in BALF and plasma histamine levels and is associated with a reduction in circulating neutrophils, eosinophils, and platelets. It is likely that antigen causes airway mast cells to release mediators that move down a concentration gradient from the airways to the pulmonary circulation.

scholarly journals Selective Inhibition of the C-Domain of ACE (Angiotensin-Converting Enzyme) Combined With Inhibition of NEP (Neprilysin): A Potential New Therapy for Hypertension

Hypertension ◽  
2021 ◽  
Author(s):  
Rhéure Alves-Lopes ◽  
Augusto C. Montezano ◽  
Karla B. Neves ◽  
Adam Harvey ◽  
Francisco J. Rios ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Converting Enzyme ◽  
Systolic Blood Pressure ◽  
Vascular Permeability ◽  
Ace Inhibitor ◽  
Endothelial Permeability ◽  
Selective Inhibition ◽  
Neutral Endopeptidase ◽  
Plasma Extravasation ◽  
Converting Enzyme

Combined inhibition of NEP (neutral endopeptidase) and ACE (angiotensin-converting enzyme), without unwanted effects, remains an attractive therapeutic strategy in cardiovascular medicine. Omapatrilat, a dual NEP inhibitor–ACE inhibitor, was a promising antihypertensive drug but failed in trials due to angioedema, an effect possibly caused by inhibition of both the N- and C-domains of ACE. Here, we aimed to determine whether lisinopril-tryptophan (lisW-S), a C-domain specific ACE inhibitor that preserves the N-domain catalytic activity, together with sacubitril (NEP inhibitor), differentially influences cardiovascular function and vascular permeability in hypertension compared with omapatrilat and lisinopril+sacubitril which inhibits both the ACE C- and N-domains. Ang II (angiotensin II)–dependent hypertensive mice (transgenic mice expressing active human renin in the liver [also known as LinA3]) received vehicle, sacubitril, lisW-S, lisinopril, lisinopril+sacubitril, or lisW-S+sacubitril for 4 weeks. Systolic blood pressure was increased in LinA3 mice, along with cardiac hypertrophy/dysfunction, impaired endothelium-dependent vasorelaxation, hypercontractile responses, vascular remodeling, and renal inflammation. LisW-S+sacubitril, lisinopril+sacubitril, and omapatrilat reduced systolic blood pressure and normalized cardiovascular remodeling and vascular hypercontractile responses in LinA3 mice. Although lisinopril+sacubitril and omapatrilat improved Ach-induced vasorelaxation, lisW-S+sacubitril had no effect. Endothelial permeability (Evans Blue assessment) was increased in omapatrilat but not in LisW-S+sacubitril–treated mice. In conclusion, lisW-S combined with sacubitril reduced systolic blood pressure and improved cardiac dysfunction in LinA3 mice, similar to omapatrilat but without effects on endothelium-dependent vasorelaxation. Moreover, increased vascular leakage (plasma extravasation) induced by omapatrilat was not evident in mice treated with lisW-S+sacubitril. Targeting ACE C-domain and NEP as a combination therapy may be as effective as omapatrilat in lowering systolic blood pressure, but without inducing vascular permeability and endothelial injury.

Human urotensin-II enhances plasma extravasation in specific vascular districts in Wistar rats

2004 ◽  
Vol 82 (1) ◽  
pp. 16-21 ◽  
Author(s):  
Gabrielle Gendron ◽  
Bryan Simard ◽  
Fernand Gobeil, Jr. ◽  
Pierre Sirois ◽  
Pedro D'Orléans-Juste ◽  
...  
Keyword(s):  
Vascular Permeability ◽  
Evans Blue ◽  
Wistar Rats ◽  
Platelet Activating Factor ◽  
Optimal Dose ◽  
Blue Dye ◽  
Plasma Extravasation ◽  
Urotensin Ii ◽  
Evans Blue Dye

Plasma extravasation (PE) was measured in adult Wistar rats by injecting Evans blue dye (EB) (20 mg kg–1) intravenously in the absence or presence of human urotensin II (U-II) (0.1–10 nmol kg–1). A consistent increase of PE was observed in specific organs (e.g., aorta, from 28.1 ± 2.4 to 74.6 ± 3.6 µg EB g–1 dry tissue; P < 0.001) after an administration of 4.0 nmol kg–1 (a preselected optimal dose) of U-II. The effects of U-II (4.0 nmol kg–1) were compared with those of endothelin-1 (ET-1) (1.0 nmol kg–1). In the thoracic aorta and pancreas, U-II was active, while ET-1 was not. The two agents were equivalent in the heart and kidney, whereas, in the duodenum, ET-1 was more active than U-II. Increases of plasma extravasation induced by U-II, but not by ET-1, were reduced after treatment with [Orn8]U-II (0.3 µmol kg–1). This latter antagonist did not show any significant residual agonistic activity in vivo in the rat. Other specific receptor antagonists for ET-1, such as BQ-123 (endothelin type A (ETA) receptor) and BQ-788 (endothelin type B (ETB) receptor), and for the platelet activating factor (PAF), such as BN50730, failed to modify the action of U-II. The present study is the first report describing the modulator roles of U-II on vascular permeability in specific organs. Moreover, the action of U-II appears specific, since it is independent of the ET-1 and PAF signalling pathways.Key words: urotensin-II, receptors antagonists, Evans blue dye, vascular permeability, rats.

Ultrastructural evidence for mast cell-macrophage interrelationships in the dura mater of the rat: Infrequent mast cell-nerve associations

1990 ◽  
Vol 48 (3) ◽  
pp. 352-353
Author(s):  
Ruth V.W. Dimlich
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Dura Mater ◽  
Spatial Relationship ◽  
Potassium Phosphate ◽  
Plasma Extravasation ◽  
Close Spatial Relationship ◽  
Male Wistar Rats ◽  
Headache Pain ◽  
Relationship Of

Mast cells in the dura mater of the rat may play a role in cerebral pathologies including neurogenic inflammation (vasodilation; plasma extravasation) and headache pain . As has been suggested for other tissues, dural mast cells may exhibit a close spatial relationship to nerves. There has been no detailed ultrastructural description of mast cells in this tissue; therefore, the goals of this study were to provide this analysis and to determine the spatial relationship of mast cells to nerves and other components of the dura mater in the rat.Four adult anesthetized male Wistar rats (290-400 g) were fixed by perfusion through the heart with 2% glutaraldehyde and 2.8% paraformaldehyde in a potassium phosphate buffer (pH 7.4) for 30 min. The head of each rat was removed and stored in fixative for a minimum of 24 h at which time the dural coverings were removed and dissected into samples that included the middle meningeal vasculature. Samples were routinely processed and flat embedded in LX 112. Thick (1 um) sections from a minimum of 3 blocks per rat were stained with toluidine blue (0.5% aqueous).

Mast Cells Can Mediate Vascular Permeability through Regulation of the PI3K–HIF-1α–VEGF Axis

2008 ◽  
Vol 178 (8) ◽  
pp. 787-797 ◽  
Author(s):  
Kyung Sun Lee ◽  
So Ri Kim ◽  
Seoung Ju Park ◽  
Kyung Hoon Min ◽  
Ka Young Lee ◽  
...  
Keyword(s):  
Mast Cells ◽  
Vascular Permeability

Secretion and activity of histamine and serotonin during cold adaptation

1963 ◽  
Vol 204 (3) ◽  
pp. 520-522 ◽  
Author(s):  
Jacques Leblanc
Keyword(s):  
Blood Pressure ◽  
Mast Cells ◽  
Urinary Excretion ◽  
Cold Adaptation ◽  
Cardiovascular Response ◽  
Blood Pressure Response ◽  
Abdominal Skin ◽  
Normal Limits ◽  
Urinary Levels ◽  
Normal Sensitivity

The urinary excretion of histamine was found to rise rapidly in rats exposed to cold (6 C). A sevenfold increase above normal is maintained during the 1st month of exposure, but during the 2nd month a decline from these high values is observed, and after 1 year the urine histamine is within normal limits. Similarly, a marked increase in the number of mast cells in the abdominal skin is observed during the first 2 months of cold exposure with a return to initial values by the 4th month. The blood pressure response to intravenous histamine is decreased during the 1st month of cold adaptation but after 1 year in the cold normal sensitivity to histamine is re-established. The excretion of 5-hydroxytryptamine is also rapidly increased during cold adaptation but no decline with time was observed. These findings obtained with histamine are compared with those found previously with noradrenaline. Whereas the urinary levels of these amines show similar variations during cold adaptation, the cardiovascular response differs. The sensitivity to histamine is decreased with increased excretion and the response to noradrenaline increased with increased secretion.

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