Neurogenic plasma extravasation: inhibition by morphine in guinea pig airways in vivo

1989 ◽  
Vol 66 (1) ◽  
pp. 268-272 ◽  
Author(s):  
M. G. Belvisi ◽  
D. F. Rogers ◽  
P. J. Barnes
Keyword(s):  
Sensory Nerve ◽  
Inhibitory Effect ◽  
Blue Dye ◽  
Plasma Extravasation ◽  
Plasma Exudation ◽  
Opioid Drugs ◽  
Similar Inhibitory Effect ◽  
Plasma Leakage ◽  
Human Airways

Opioid drugs have been shown to inhibit neurogenic plasma exudation in skin by a presynaptic mechanism. We determined whether a similar inhibitory effect operates in the airways of anesthetized guinea pigs in vivo with the use of Evans blue dye as a marker of plasma leakage. Stimulation of the vagus nerve significantly increased leakage of dye in trachea and main bronchi (by approximately 300 and 600%, respectively). Similar increases in leakage were seen in the presence of atropine and propranolol. Morphine (1–30 mg/kg iv) inhibited leakage in a dose-related manner with complete inhibition in the trachea at a dose of 30 mg/kg. The inhibition was blocked by the opioid receptor-antagonist naloxone (1 mg/kg iv). Intravenous substance P significantly increased leakage but was not inhibited by morphine. We conclude that morphine inhibits neurogenic plasma leakage by presynaptic inhibition of release of neuropeptides from sensory nerve endings. If similar mechanisms are operative in human airways, inhibition of neurogenic plasma leakage by opioid drugs devoid of central effects may be of value in the therapy of asthma.

Imaging inflammatory plasma leakage in vivo

2011 ◽  
Vol 105 (05) ◽  
pp. 783-789 ◽  
Author(s):  
Lennart Lindbom ◽  
Ellinor Kenne
Keyword(s):  
Vascular Permeability ◽  
Near Infrared ◽  
Imaging Techniques ◽  
Intravital Imaging ◽  
Plasma Extravasation ◽  
Optical Techniques ◽  
Affected Tissue ◽  
Plasma Leakage ◽  
Near Infrared Fluorescence Imaging

SummaryIncreased vascular permeability and consequent plasma leakage from postcapillary venules is a cardinal sign of inflammation. Although the movement of plasma constituents from the vasculature to the affected tissue aids in clearing the inflammatory stimulus, excessive plasma extravasation can lead to hospitalisation or death in cases such as influenza-induced pneumonia, burns or brain injury. The use of intravital imaging has significantly contributed to the understanding of the mechanisms controlling the vascular permeability alterations that occur during inflammation. Today, intravital imaging can be performed using optical and non-optical techniques. Optical techniques, which are generally used in experimental settings, include traditional intravital fluorescence microscopy and near-infrared fluorescence imaging. Magnetic resonance (MRI) and radioisotopic imaging are used mainly in the clinical setting, but are increasingly used in experimental work, and can detect plasma leakage without optics. Although these methods are all able to visualise inflammatory plasma leakage in vivo, the spatial and temporal resolution differs between the techniques. In addition, they vary with regards to invasiveness and availability. This overview discusses the use of imaging techniques in the visualisation of inflammatory plasma leakage.

Esophageal stimulation by hydrochloric acid causes neurogenic inflammation in the airways in guinea pigs

1997 ◽  
Vol 82 (3) ◽  
pp. 738-745 ◽  
Author(s):  
Junji Hamamoto ◽  
Hirotsugu Kohrogi ◽  
Osamu Kawano ◽  
Hajime Iwagoe ◽  
Kazuhiko Fujii ◽  
...  
Keyword(s):  
Hydrochloric Acid ◽  
Evans Blue ◽  
Guinea Pigs ◽  
Neurogenic Inflammation ◽  
Neutral Endopeptidase ◽  
Blue Dye ◽  
Plasma Extravasation ◽  
Neural Pathways ◽  
Plasma Leakage ◽  
Stimulation Of

Hamamoto, Junji, Hirotsugu Kohrogi, Osamu Kawano, Hajime Iwagoe, Kazuhiko Fujii, Nahomi Hirata, and Masayuki Ando.Esophageal stimulation by hydrochloric acid causes neurogenic inflammation in the airways in guinea pigs. J. Appl. Physiol. 82(3): 738–745, 1997.—To investigate whether tachykinins are released in the airways in response to stimulation of the esophagus, we studied the airway plasma extravasation induced by intraesophageal HCl in the presence or absence of neutral endopeptidase inhibitor phosphoramidon and NK1-receptor antagonist FK-888 in anesthetized guinea pigs. The airway plasma leakage was evaluated by measuring extravasated Evans blue dye in the animals pretreated with propranolol and atropine. Infusion of 1 N HCl into the esophagus significantly increased plasma extravasation in the trachea. Phosphoramidon significantly potentiated plasma extravasation in the trachea and main bronchi, whereas FK-888 significantly inhibited that extravasation in a dose-related manner. In the capsaicin-treated animals, airway plasma extravasation was completely inhibited even in the presence of phosphoramidon. Tracheal plasma extravasation potentiated by phosphoramidon was significantly inhibited in the bilateral vagotomized animals. These results suggest that 1) tachykinin-like substances are released to cause plasma extravasation in the airways as a result of intraesophageal HCl stimulation and 2) there are neural pathways communicating between the esophagus and airways, including the vagus nerve.

Effects and interactions of opioids on plasma exudation induced by cigarette smoke in guinea pig bronchi

1999 ◽  
Vol 276 (3) ◽  
pp. L391-L397 ◽  
Author(s):  
Yu-Hong Lei ◽  
Duncan F. Rogers
Keyword(s):  
Guinea Pig ◽  
Cigarette Smoke ◽  
Opioid Receptor ◽  
Blue Dye ◽  
Endogenous Histamine ◽  
Opioid Receptor Agonist ◽  
Plasma Exudation ◽  
Μ Opioid Receptor ◽  
Air Control

The effects of opioids on cigarette smoke-induced plasma exudation were investigated in vivo in the main bronchi of anesthetized guinea pigs, with Evans blue dye as a plasma marker. Acute inhalation of cigarette smoke increased plasma exudation by 216% above air control values. Morphine, 0.1–10 mg/kg but not 30 mg/kg, inhibited the exudation but had no significant effect on substance P-induced exudation. Both 10 and 30 mg/kg of morphine increased exudation in air control animals, an effect inhibited by antihistamines but not by a tachykinin neurokinin type 1-receptor antagonist. Naloxone inhibited all morphine responses. Cigarette smoke-induced plasma exudation was inhibited by a μ-opioid-receptor agonist (DAMGO) but not by agonists at δ (DPDPE)- or κ (U-50488H)-receptors. None of these agonists affected exudation in air control animals. DPDPE prevented the inhibition by DAMGO of cigarette smoke-induced plasma exudation, and the combination of DAMGO and DPDPE increased exudation in air control animals. Prevention of inhibition and the combination-induced increase were inhibited by antihistamines or the mast cell-stabilizing drug sodium cromoglycate. U-50488H did not alter the response to either DAMGO or DPDPE. We conclude that, in guinea pig main bronchi in vivo, μ-opioid-receptor agonists inhibit cigarette smoke-induced plasma exudation via a prejunctional mechanism. Plasma exudation induced by μ- and δ-receptor interactions is due to endogenous histamine release from mast cells.

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.

Nifedipine increases microvascular permeability via a direct local effect on postcapillary venules

1998 ◽  
Vol 275 (4) ◽  
pp. H1388-H1394 ◽  
Author(s):  
Morteza Taherzadeh ◽  
Asit K. Das ◽  
John B. Warren
Keyword(s):  
Calcium Channel ◽  
Calcium Channel Antagonist ◽  
Local Effect ◽  
Blue Dye ◽  
Cremaster Muscle ◽  
Rat Skin ◽  
Rat Skeletal Muscle ◽  
Postcapillary Venule ◽  
Plasma Leakage

Calcium-channel antagonist drugs are prescribed widely for angina and hypertension. A limiting side effect is edema, which can make heart failure worse. We show that nifedipine, a dihydropyridine-type calcium-channel antagonist, can increase vascular permeability in rat skeletal muscle and skin when injected locally. In nifedipine-injected cremaster muscle, the copper content, used to quantify Monastral blue dye accumulation, was 15.0 ± 2.4 μg/g compared with 5.3 ± 0.7 μg/g in control preparations ( P < 0.05). The injection of nifedipine in rat skin in vivo increased local plasma leakage in injected sites from 5.5 ± 1.1 μl in control sites to 9.9 ± 2.5, 17.0 ± 2.4, 24.3 ± 5.9, and 23.3 ± 5.4 μl in sites injected with 10−10, 10−9, 10−8, or 10−7.2 mol/site, respectively ( P < 0.05 in each case compared with control). Vascular labeling techniques using light microscopy, electron microscopy, and microanalysis show that the microvascular site of leakage is not from capillaries but from postcapillary venules of 12–36 μm in diameter, the same site that controls the edema response in inflammation. Nifedipine can act within the microcirculation to increase the permeability of the postcapillary venule.

Neuropeptide Y inhibits neurogenic inflammation in guinea pig airways

1993 ◽  
Vol 75 (1) ◽  
pp. 103-107 ◽  
Author(s):  
T. Takahashi ◽  
M. Ichinose ◽  
H. Yamauchi ◽  
M. Miura ◽  
N. Nakajima ◽  
...  
Keyword(s):  
Substance P ◽  
Neuropeptide Y ◽  
Evans Blue ◽  
Neurogenic Inflammation ◽  
Sensory Nerve ◽  
Blue Dye ◽  
Plasma Extravasation ◽  
Dependent Manner ◽  
Evans Blue Dye ◽  
Exogenous Substance

We examined the effect of neuropeptide Y (NPY) on neurogenic airway microvascular leakage. Male Dunkin-Hartley guinea pigs (250–350 g) were anesthetized with urethan (2 g/kg ip). The cervical artery and vein were cannulated for monitoring blood pressure and injecting drugs, respectively. Atropine and propranolol (each 1 mg/kg i.v.) were administered 30 min before the experiment. After pretreatment with saline (vehicle for NPY) or NPY (1–100 micrograms/kg i.v.), Evans blue dye (30 mg/kg iv) was administered. Then, bilateral vagal nerves were electrically stimulated (5 V, 7 Hz, 5-ms duration for 3 min) to induce airway plasma leakage. Airways were divided into four sections [trachea (Tr), main bronchi, central intrapulmonary airways (IPA), and peripheral IPA] and incubated in formamide (37 degrees C for 16 h). The concentration of Evans blue dye was measured by spectrophotometer. Furthermore, we examined the effect of NPY on exogenous substance P- (0.3 microgram/kg i.v.) induced plasma extravasation. Bilateral vagal stimulation significantly increased leakage of dye in Tr to peripheral IPA. NPY did not affect basal leakage but did significantly inhibit neurogenic plasma extravasation in a dose-dependent manner with maximal inhibitions of 42.3 (Tr), 67.7 (main bronchi), 38.2 (central IPA), and 26.3% (peripheral IPA) at 30 micrograms/kg. Exogenous substance P-induced plasma extravasation was not inhibited by NPY. We conclude that NPY inhibits neurogenic inflammation by prejunctional inhibition of neuropeptide release from airway sensory nerve terminals.

Effect of T-kinin on microvascular permeability and its modulation by peptidases in rat airways

1995 ◽  
Vol 79 (4) ◽  
pp. 1129-1133 ◽  
Author(s):  
I. Yamawaki ◽  
J. Tamaoki ◽  
Y. Takeda ◽  
A. Chiyotani ◽  
N. Sakai ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Receptor Antagonist ◽  
Enzyme Inhibitor ◽  
Sensory Nerve ◽  
Neutral Endopeptidase ◽  
Rat Plasma ◽  
Plasma Extravasation ◽  
Dependent Manner ◽  
Converting Enzyme

T-kinin (Ile-Ser-bradykinin), the product of T-kininogen, has been found in rat plasma during systemic inflammation, but the effect of this kinin on airway inflammatory response is unknown. We examined the effect of T-kinin on vascular permeability in airways of anesthetized rats in vivo by using photometric measurement of the extravasated Evans blue. Intravenous injection of T-kinin (0.1–10 mumol/kg) increased dye extravasation in a dose-dependent manner, with 134% for trachea and 117% for bronchi by 1 mumol/kg. Pretreatment with bradykinin B2-receptor antagonist Hoe-140 (100 nmol/kg), but not the B1-receptor antagonist des-Arg9-Leu8-bradykinin (5 mg/kg), abolished plasma extravasation evoked by T-kinin (1 mumol/kg). NK1 tachykinin-receptor antagonist CP-99994 (4 mg/kg) did not affect T-kinin-induced vascular leakage. Pretreatment with captopril (2.5 mg/kg), angiotensin-converting enzyme inhibitor, potentiated T-kinin (100 nmol/kg)-induced plasma extravasation, whereas phosphoramidon (2.5 mg/kg), a neutral endopeptidase inhibitor, had no effect. We conclude that T-kinin produces airway vascular extravasation via stimulation of B2 receptors. The effect is modulated by endogenous angiotensin-converting enzyme and is not mediated via activation of sensory nerve.

The Inhibition of Platelet Aggregation by an Aorta Intima Extract

1974 ◽  
Vol 32 (02/03) ◽  
pp. 417-431 ◽  
Author(s):  
A. du P Heyns ◽  
D. J van den Berg ◽  
G. M Potgieter ◽  
F. P Retief
Keyword(s):  
Platelet Aggregation ◽  
Degradation Products ◽  
Adenosine Diphosphate ◽  
Inhibitory Effect ◽  
Protective Role ◽  
Vascular Trauma ◽  
Wear And Tear ◽  
Sequential Addition ◽  
Aggregation Activity

SummaryThe platelet aggregating activity of extracts of different layers of the arterial wall was compared to that of Achilles tendon. Arterial media and tendon extracts, adjusted to equivalent protein content as an index of concentration, aggregated platelets to the same extent but an arterial intima extract did not aggregate platelets. Platelet aggregation induced by collagen could be inhibited by mixing with intima extract, but only to a maximum of about 80%. Pre-mixing adenosine diphosphate (ADP) with intima extracts diminished the platelet aggregation activity of the ADP. Depending on the relationship between ADP and intima extract concentrations aggregating activity could either be completely inhibited or inhibition abolished. Incubation of ADP with intima extract and subsequent separation of degradation products by paper chromatography, demonstrated a time-dependent breakdown of ADP with AMP, adenosine, inosine and hypoxanthine as metabolic products; ADP removal was complete. Collagen, thrombin and adrenaline aggregate platelets mainly by endogenous ADP of the release reaction. Results of experiments comparing inhibition of aggregation caused by premixing aggregating agent with intima extract, before exposure to platelets, and the sequential addition of first the intima extract and then aggregating agent to platelets, suggest that the inhibitory effect of intima extract results from ADP breakdown. It is suggested that this ADP degradation by intima extract may play a protective role in vivo by limiting the size of platelet aggregates forming at the site of minimal “wear and tear” vascular trauma.

Measurement of the Platelet Response to Laser- induced Microvascular Injury

1974 ◽  
Vol 32 (02/03) ◽  
pp. 704-713 ◽  
Author(s):  
F. N McKenzie ◽  
K.-E Arfors ◽  
N. A Matheson
Keyword(s):  
Inhibitory Effect ◽  
Microvascular Blood Flow ◽  
Platelet Response ◽  
High Concentration ◽  
Platelet Activity ◽  
Microvascular Injury ◽  
Arterial Blood ◽  
Proximal Site ◽  
Adenosine Phosphates

SummaryA study has been made of the biochemical factors underlying the platelet response to laser-induced microvascular injury. A platelet aggregating substance is produced at sites of laser-induced injury which markedly stimulates platelet activity at a site of injury inflicted a short distance downstream. Distal sites of injury are not similarly influenced if the distance between the injuries is increased or if the proximal site no longer shows platelet-stimulating activity. The stimulating effect of an adjacent proximal injury on platelet activity at a distal site is inhibited by local intra-arterial infusion of adenosine. Measurements of arterial blood pressure and microvascular blood flow velocity during adenosine infusion showed that its inhibitory effect on platelet activity is largely independent of its vasodilator properties. The effect of infusion of different adenosine phosphates (AMP, ADP, ATP) was also studied. Very small amounts of ADP markedly stimulated platelet activity and the emboli formed were similar to those normally produced at sites of laser injury. At high concentration AMP inhibited while ATP stimulated platelet activity in vivo. The results emphasise the fundamental role of ADP as a mediator of the platelet response at sites of laser- induced microvascular injury.

The Effects of Heparin and Annexin V on Fibrin Accretion after Injury in the Jugular Veins of Rabbits

1993 ◽  
Vol 69 (03) ◽  
pp. 227-230 ◽  
Author(s):  
J Van Ryn-McKenna ◽  
H Merk ◽  
T H Müller ◽  
M R Buchanan ◽  
W G Eisert
Keyword(s):  
Vessel Wall ◽  
Thrombin Generation ◽  
Antithrombin Iii ◽  
Specific Effect ◽  
Annexin V ◽  
Inhibitory Effect ◽  
Jugular Veins ◽  
Prothrombinase Complex ◽  
Wall Injury

SummaryWe compared the relative abilities of unfractionated heparin and annexin V to prevent fibrin accretion onto injured jugular veins in vivo. Heparin was used to accelerate the inhibition of thrombin by antithrombin III, and annexin V was used to inhibit the assembly of the prothrombinase complex on phospholipid surfaces, thereby blocking thrombin generation. Rabbit jugular veins were isolated in situ, a 2 cm segment was injured by perfusing it with air, and then blood flow was re-established. Five minutes later, each rabbit was injected with heparin (20 U/kg) or annexin V (0.3 mg/kg) and then with 125I-fibrinogen. The amount of 125I-fibrin accumulation onto each injured vessel wall segment was measured 4 h later. Each injured vessel was completely deendothelialized as a result of the air perfusion as demonstrated by electron microscopy. 125I-fibrin accretion onto the injured jugular veins was enhanced 2.4-fold as compared to the uninjured veins in sham-operated animals. Heparin treatment did not reduce fibrin accretion, whereas, annexin V treatment decreased fibrin accretion by 60%, p <0.05. This latter effect was achieved without sustained circulating anticoagulation. Additional experiments confirmed that the inhibitory effect of annexin V on fibrin accretion was associated with a surface specific effect, since more annexin V bound to the injured jugular vein segments as compared to the non-injured jugular veins. We conclude that, i) mild vessel wall injury (selective de-endothelialization) in veins results in a thrombogenic vessel wall; ii) the thrombogenecity of which is not inhibited by prophylactic doses of heparin; but iii) is inhibited by annexin V, which binds to injured vessel wall surface, and inhibits thrombin generation independently of antithrombin III.

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