Mechanisms of T-kinin-induced increases in macromolecule extravasation in vivo

1993 ◽  
Vol 74 (6) ◽  
pp. 2896-2903 ◽  
Author(s):  
X. P. Gao ◽  
W. G. Mayhan ◽  
J. M. Conlon ◽  
S. I. Rennard ◽  
I. Rubinstein
Keyword(s):  
Mast Cells ◽  
Fluorescein Isothiocyanate ◽  
Cheek Pouch ◽  
Site Formation ◽  
Plasma Extravasation ◽  
Bradykinin Receptors ◽  
Hamster Cheek Pouch ◽  
Peripheral Microcirculation ◽  
Neurokinin 1

The purpose of this study was to investigate the mechanisms that mediate T-kinin- (Ile-Ser-bradykinin) induced increases in macromolecule extravasation in the hamster cheek pouch. Changes in plasma extravasation were quantified by counting the number of leaky sites and calculating the clearance of fluorescein isothiocyanate- (FITC) dextran (mol mass = 70 kDa) during suffusion of the cheek pouch with T-kinin (0.1–1.0 microM) by using intravital microscopy. T-kinin induced a significant time- and concentration-dependent increase in leaky site formation and clearance of FITC-dextran (P < 0.05). The increase in plasma extravasation in response to T-kinin was mediated by two mechanisms: a COOH-terminal-mediated stimulation of B2 bradykinin receptors in postcapillary venules and an NH2-terminal-mediated degranulation of mast cells leading to histamine release. Indomethacin and CP 96345, a selective nonpeptide neurokinin-1 receptor antagonist, had no significant effects on T-kinin-induced responses. We conclude that T-kinin increases macromolecule extravasation in the peripheral microcirculation by stimulating B2 bradykinin receptors in post-capillary venules and by degranulating mast cells.

Neurogenic plasma exudation mediates grain dust-induced tissue injury in vivo

1997 ◽  
Vol 272 (2) ◽  
pp. R475-R481 ◽  
Author(s):  
X. P. Gao ◽  
S. Von Essen ◽  
I. Rubinstein
Keyword(s):  
Oral Mucosa ◽  
Tissue Injury ◽  
Fluorescein Isothiocyanate ◽  
Grain Sorghum ◽  
Cheek Pouch ◽  
Site Formation ◽  
Hamster Cheek Pouch ◽  
Plasma Exudation ◽  
Neurokinin 1

The purpose of this study was to determine whether an aqueous extract of grain sorghum dust (GDE) elicits neurogenic plasma exudation in the oral mucosa in vivo. Using intravital microscopy, we found that GDE elicited significant, concentration-dependent leaky site formation and an increase in clearance of fluorescein isothiocyanate-labeled dextran (FITC-dextran; mol mass 70 kDa) from the hamster cheek pouch (P < 0.05). The selective, nonpeptide neurokinin(1) (substance P) receptor antagonists, CP-96,345 and RP-67580, but not the 2R,3R enantiomer CP-96,344, significantly attenuated GDE-induced leaky site formation and increase in clearance of FITC-dextran (P < 0.05). Indomethacin had no significant effects on GDE-induced responses. CP-96,345 had no significant effects of adenosine-induced leaky site formation and increase in clearance of FITC-dextran from the cheek pouch. We conclude that GDE elicits neurogenic plasma exudation from the oral mucosa in vivo. We suggest that this process is one mechanism whereby grain sorghum dust elicits immediate oral mucosa inflammation in vivo.

Tannic acid elicits neurogenic plasma exudation from the in situ hamster cheek pouch

1998 ◽  
Vol 274 (1) ◽  
pp. R237-R242
Author(s):  
Xiao-Pei Gao
Keyword(s):  
Tannic Acid ◽  
Biosynthetic Pathway ◽  
Fluorescein Isothiocyanate ◽  
Cheek Pouch ◽  
Site Formation ◽  
Hamster Cheek Pouch ◽  
Plasma Exudation ◽  
Synthase Inhibitor

The purpose of this study was to determine whether tannic acid elicits neurogenic plasma exudation from the oral mucosa in vivo and, if so, whether this response is transduced in part by thel-arginine-nitric oxide (NO) biosynthetic pathway. Using intravital microscopy, we found that suffusion of tannic acid elicits significant concentration-dependent leaky site formation and increase in clearance of fluorescein isothiocyanate-dextran (molecular mass 70 kDa) from the in situ hamster cheek pouch ( P < 0.05). These effects are significantly attenuated by two selective, but structurally distinct, nonpeptide neurokinin-1 (NK1) receptor antagonists, CP-96,345 and RP-67580, but not by CP-96,344, the 2R,3R enantiomer of CP-96,345. N G-nitrol-arginine methyl ester (l-NAME), an NO synthase inhibitor, but notd-NAME, significantly attenuates tannic acid-induced responses.l-Arginine, but notd-arginine, reverses the attenuating effects of l-NAME. We conclude that tannic acid elicitsl-arginine-NO biosynthetic pathway-dependent neurogenic plasma exudation from the in situ hamster cheek pouch.

scholarly journals Dexamethasone attenuates acute macromolecular efflux increase evoked by smokeless tobacco extract

1999 ◽  
Vol 87 (2) ◽  
pp. 619-625 ◽  
Author(s):  
Xiao-Pei Gao ◽  
Syed R. Akhter ◽  
Hiroyuki Ikezaki ◽  
Dennis Hong ◽  
Israel Rubinstein
Keyword(s):  
Oral Mucosa ◽  
Smokeless Tobacco ◽  
Fluorescein Isothiocyanate ◽  
Cheek Pouch ◽  
Site Formation ◽  
Hamster Cheek Pouch ◽  
Acute Increase ◽  
Tobacco Extract

The purpose of this study was to determine whether dexamethasone attenuates the acute increase in macromolecular efflux from the oral mucosa elicited by an aqueous extract of smokeless tobacco (STE) in vivo, and, if so, whether this response is specific. Using intravital microscopy, we found that 20-min suffusion of STE elicited significant, concentration-related leaky site formation and an increase in clearance of fluorescein isothiocyanate-labeled dextran (FITC-dextran; mol mass 70 kDa) from the in situ hamster cheek pouch ( P < 0.05). This response was significantly attenuated by dexamethasone (10 mg/kg iv). Dexamethasone also attenuated the bradykinin-induced leaky site formation and the increase in clearance of FITC-dextran from the cheek pouch. However, it had no significant effects on adenosine-induced responses. Dexamethasone had no significant effects on baseline arteriolar diameter and on bradykinin-induced vasodilation in the cheek pouch. Collectively, these data indicate that dexamethasone attenuates, in a specific fashion, the acute increase in macromolecular efflux from the in situ oral mucosa evoked by short-term suffusion of STE. We suggest that corticosteroids mitigate acute oral mucosa inflammation elicited by smokeless tobacco.

Cigarette smoke extract potentiates bradykinin-induced increases in microvascular permeability

1993 ◽  
Vol 75 (1) ◽  
pp. 27-32 ◽  
Author(s):  
W. G. Mayhan ◽  
I. Rubinstein
Keyword(s):  
Cigarette Smoke ◽  
Fluorescein Isothiocyanate ◽  
Cigarette Smoke Extract ◽  
Microvascular Permeability ◽  
Cheek Pouch ◽  
Site Formation ◽  
Hamster Cheek Pouch ◽  
Fluorescein Isothiocyanate Dextran ◽  
Macromolecular Permeability

The first goal of this study was to determine whether cigarette smoke extract (CSE) increases microvascular permeability of the hamster cheek pouch in vivo. The second goal was to determine whether CSE potentiates bradykinin-induced increases in vascular permeability in the hamster cheek pouch. Using intravital microscopy, we examined the permeability of the hamster cheek pouch to fluorescein isothiocyanate-dextran (mol wt 70,000). Increases in permeability were quantitated by counting the number of postcapillary venular leaky sites per 0.11 cm2. Superfusion of CSE (1, 5, and 10%) did not produce venular leaky sites and, thus, did not alter macromolecular permeability. Superfusion of bradykinin (0.1, 0.5, and 1.0 microM) produced a dose-related increase in the number of venular leaky sites. Formation of leaky sites in response to bradykinin was potentiated by CSE. To determine whether potentiation of bradykinin-induced leaky site formation by CSE was related to products released via the cyclooxygenase pathway, we examined the effects of pretreatment with indomethacin (10 mg/kg i.v.). Indomethacin did not alter the potentiating effect of CSE on bradykinin-induced leaky site formation. These findings suggest that CSE does not alter basal permeability of the hamster cheek pouch microcirculation in vivo. However, CSE potentiates bradykinin-induced increases in microvascular permeability. The mechanism of CSE-induced potentiation of microvascular permeability does not appear to be related to substances produced via the cyclooxygenase pathway.

scholarly journals Subtilisin Increases Macromolecular Efflux from the Oral Mucosa

2000 ◽  
Vol 7 (5) ◽  
pp. 794-802 ◽  
Author(s):  
Israel Rubinstein
Keyword(s):  
Receptor Antagonist ◽  
Oral Mucosa ◽  
Serine Proteinase ◽  
Fluorescein Isothiocyanate ◽  
Cheek Pouch ◽  
Site Formation ◽  
Induced Responses ◽  
Hamster Cheek Pouch ◽  
Neurokinin 1

ABSTRACT The purpose of this study was to determine whether subtilisin, a potent serine proteinase derived from Bacillus species contaminating smokeless tobacco, increases macromolecular efflux from the oral mucosa and, if so, whether local elaboration of bradykinin mediates this response. Using intravital microscopy, I found that suffusion of subtilisin elicits significant, concentration-dependent leaky site formation and an increase in the clearance of fluorescein isothiocyanate-labeled dextran (molecular mass, 70 kDa) from the in situ hamster cheek pouch (P < 0.05). Heat-inactivated subtilisin had no significant effects on macromolecular efflux. Subtilisin-induced responses were significantly attenuated by Hoe 140 and NPC 17647, two structurally distinct selective bradykinin B2 receptor antagonists, but not by des-Arg9-[Leu8]bradykinin, a selective bradykinin B1 receptor antagonist, or CP-96,345, a selective neurokinin-1 receptor antagonist. Aprotinin, but not leupeptin, significantly attenuated subtilisin-induced increase in macromolecular efflux. Indomethacin had no significant effects on subtilisin-induced responses. Collectively, these data indicate that subtilisin increases the macromolecular efflux from the in situ hamster cheek pouch in a catalytic-site-dependent fashion through local elaboration of bradykinin. This response does not involve the stimulation of local afferent nerves or the production of prostaglandins.

NK1 receptors mediate tachykinin-induced increase in microvascular clearance in hamster cheek pouch

1993 ◽  
Vol 265 (2) ◽  
pp. H593-H598
Author(s):  
X. P. Gao ◽  
R. A. Robbins ◽  
R. M. Snider ◽  
J. Lowe ◽  
S. I. Rennard ◽  
...  
Keyword(s):  
Substance P ◽  
Fluorescein Isothiocyanate ◽  
Cheek Pouch ◽  
Neurokinin A ◽  
Plasma Extravasation ◽  
Hamster Cheek Pouch ◽  
Neurokinin B ◽  
Dextran 70 ◽  
Fluorescein Isothiocyanate Dextran ◽  
Neurogenic Plasma Extravasation

The purpose of this study was to determine the receptor subtype(s) that mediates tachykinin-induced neurogenic plasma extravasation in the hamster cheek pouch. Changes in microvascular clearance were quantified by counting the number of leaky sites and calculating the clearance of fluorescein isothiocyanate-dextran [mol wt 70,000 (Dextran 70)] during suffusion of the cheek pouch with substance P, neurokinin A, neurokinin B, and capsaicin. Suffusion of substance P, capsaicin, and neurokinin A, but not neurokinin B, was associated with a significant concentration-dependent increase in leaky site formation and clearance of fluorescein isothiocyanate-Dextran 70 (P < 0.05). However, the responses to substance P and capsaicin were significantly greater than those to neurokinin A. Pretreatment with the selective, nonpeptide NK1 receptor antagonist, CP-96,345, significantly attenuated substance P- and capsaicin-induced but not neurokinin A-induced responses (P < 0.05). These effects were specific, since the 2R,3R enantiomer, CP-96,344, was inactive, and CP-96,345 had no significant effect on adenosine-induced responses. We conclude that, in the hamster cheek pouch, NK1 receptors are the predominant receptors that mediate neurogenic plasma extravasation.

Exogenous calmodulin potentiates vasodilation elicited by phospholipid-associated VIP in vivo

1999 ◽  
Vol 276 (5) ◽  
pp. R1359-R1365 ◽  
Author(s):  
Hiroyuki Ikezaki ◽  
Manisha Patel ◽  
Hayat Önyüksel ◽  
Syed R. Akhter ◽  
Xiao-Pei Gao ◽  
...  
Keyword(s):  
Active Sites ◽  
Calcium Ionophore ◽  
Cheek Pouch ◽  
Induced Responses ◽  
Hamster Cheek Pouch ◽  
Sterically Stabilized Liposomes ◽  
Extracellular Calmodulin ◽  
Peripheral Microcirculation

The purpose of this study was to determine whether exogenous calmodulin potentiates vasoactive intestinal peptide (VIP)-induced vasodilation in vivo and, if so, whether this response is amplified by association of VIP with sterically stabilized liposomes. Using intravital microscopy, we found that calmodulin suffused together with aqueous and liposomal VIP did not potentiate vasodilation elicited by VIP in the in situ hamster cheek pouch. However, preincubation of calmodulin with liposomal, but not aqueous, VIP for 1 and 2 h and overnight at 4°C before suffusion significantly potentiated vasodilation ( P < 0.05). Calmodulin-induced responses were significantly attenuated by calmidazolium, trifluoperazine, and N G-nitro-l-arginine methyl ester (l-NAME) but notd-NAME. The effects ofl-NAME were reversed byl- but notd-arginine. Indomethacin had no significant effects on calmodulin-induced responses. Calmodulin had no significant effects on adenosine-, isoproterenol-, acetylcholine-, and calcium ionophore A-23187-induced vasodilation. Collectively, these data indicate that exogenous calmodulin amplifies vasodilation elicited by phospholipid-associated, but not aqueous, VIP in the in situ peripheral microcirculation in a specific, calmodulin active sites-, and nitric oxide-dependent fashion. We suggest that extracellular calmodulin, phospholipids, and VIP form a novel functionally coordinated class of endogenous vasodilators.

Nitric oxide accounts for histamine-induced increases in macromolecular extravasation

1994 ◽  
Vol 266 (6) ◽  
pp. H2369-H2373 ◽  
Author(s):  
W. G. Mayhan
Keyword(s):  
Nitric Oxide ◽  
Fluorescent Microscopy ◽  
Fluorescein Isothiocyanate ◽  
Cheek Pouch ◽  
Hamster Cheek Pouch ◽  
Before And After ◽  
Subsequent Activation ◽  
Ly 83583

The goal of this study was to determine the role of nitric oxide in histamine-induced increases in macromolecular extravasation in the hamster cheek pouch in vivo. We used intravital fluorescent microscopy and fluorescein isothiocyanate dextran (FITC-dextran; mol wt = 70,000 K) to examine extravasation from postcapillary venules in response to histamine before and after application of an enzymatic inhibitor of nitric oxide, NG-monomethyl-L-arginine (L-NMMA; 1.0 microM). Increases in extravasation of macromolecules were quantitated counting the number of venular leaky sites. Histamine (1.0 and 5.0 microM) increased the number of venular leaky sites from zero (basal conditions) to 11 +/- 1 and 21 +/- 2/0.11 cm2, respectively. Superfusion of L-NMMA (1.0 microM) and LY-83583 (1.0 microM) significantly decreased histamine-induced formation of venular leaky sites, whereas L-arginine (100 microM) potentiated histamine-induced formation of venular leaky sites. In contrast, superfusion of NG-monomethyl-D-arginine (1.0 microM) did not inhibit the formation of venular leaky sites in response to histamine. Thus the findings of the present study suggest that production of nitric oxide, and subsequent activation of guanylate cyclase, plays an important role in macromolecular efflux in vivo in response to histamine.

Loop diuretics attenuate bradykinin-induced increase in clearance of macromolecules in the oral mucosa

1996 ◽  
Vol 80 (3) ◽  
pp. 818-823 ◽  
Author(s):  
X. P. Gao ◽  
J. M. Conlon ◽  
J. K. Vishwanatha ◽  
R. A. Robbins ◽  
I. Rubinstein
Keyword(s):  
Oral Mucosa ◽  
Fluorescein Isothiocyanate ◽  
Loop Diuretics ◽  
Cheek Pouch ◽  
Site Formation ◽  
Induced Responses ◽  
Vasomotor Tone ◽  
Hamster Cheek Pouch ◽  
Significant Concentration

The purpose of this study was to determine whether loop diuretics attenuate bradykinin-induced increase in clearance of macromolecules in the oral mucosa in situ and, if so, to start to determine the mechanisms that mediated these responses. By using intravital microscopy, we found that bradykinin induced a significant concentration-dependent increase in fluorescein isothiocyanate-labeled dextran (mol mass 70 kDa) leaky site formation in the hamster cheek pouch. These responses were significantly attenuated by topical application of two structurally distinct loop diuretics, furosemide and ethacrynic acid, onto the cheek pouch (P < 0.05). Hydrochlorothiazide, a nonloop diuretic, had no significant effects on bradykinin-induced responses. Furosemide had no significant effects on adenosine-induced leaky site formation. Application of bradykinin after furosemide, but not after hydrochlorothiazide, was associated with a significant concentration-dependent decrease in bradykinin-like immunoreactivity in the cheek pouch suffusate (P < 0.05). Prostaglandins and changes in vasomotor tone did not modulate the effects of furosemide on bradykinin-induced responses. These data indicate that loop diuretics attenuate bradykinin-induced increase in clearance of macromolecules in the oral mucosa in a specific fashion, probably by amplifying local bradykinin catabolism. We suggest that topical loop diuretics could be useful in the treatment of oral mucosa inflammation elicited by bradykinin.

Interleukin-1 beta potentiates bradykinin-induced macromolecular efflux from hamster oral mucosa

1997 ◽  
Vol 272 (1) ◽  
pp. R294-R301
Author(s):  
X. P. Gao ◽  
I. Rubinstein
Keyword(s):  
Receptor Antagonist ◽  
Oral Mucosa ◽  
Interleukin 1 ◽  
Fluorescein Isothiocyanate ◽  
Cheek Pouch ◽  
Site Formation ◽  
Interleukin 1 Beta ◽  
Vasomotor Tone ◽  
Hamster Cheek Pouch

The purpose of this study was to determine whether interleukin-1 beta (IL-1 beta) elicits macromolecular efflux from the in situ oral mucosa and whether it amplifies that evoked by bradykinin. Using intravital microscopy, we found that suffusion of recombinant human IL-1 beta (50 ng/ml) had no significant effects on leaky site formation and increase in clearance of fluorescein isothiocyanate-labeled dextran (mol mass 70 kDa) from the hamster cheek pouch. However, it significantly potentiated bradykinin-induced macromolecular efflux (P < 0.05). The potentiating effects of IL-1 beta on bradykinin-induced responses were abrogated by a bradykinin B2-receptor antagonist and by a recombinant human IL-1-receptor antagonist. They were not mediated by substance P, prostaglandins, or changes in vasomotor tone. IL-1 beta had no significant effects on adenosine-induced macromolecular efflux. Collectively, these data indicate that IL-1 beta potentiates bradykinin-induced macromolecular efflux from the in situ hamster oral mucosa in a specific fashion. We suggest that this interaction could play a role in the pathogenesis of oral mucosa inflammation.

Sign in / Sign up

Export Citation Format

Share Document