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.

scholarly journals Purified ACE attenuates smokeless tobacco-induced increase in macromolecular efflux from the oral mucosa

1997 ◽  
Vol 83 (1) ◽  
pp. 74-81 ◽  
Author(s):  
Xiao-Pei Gao ◽  
Hideyuki Suzuki ◽  
Christopher O. Olopade ◽  
Sergei Pakhlevaniants ◽  
Israel Rubinstein
Keyword(s):  
Oral Mucosa ◽  
Smokeless Tobacco ◽  
Fluorescein Isothiocyanate ◽  
Cheek Pouch ◽  
Site Formation ◽  
Hamster Cheek Pouch ◽  
Rabbit Lung ◽  
Angiotensin I Converting Enzyme ◽  
Tobacco Extract

Gao, Xiao-pei, Hideyuki Suzuki, Christopher O. Olopade, Sergei Pakhlevaniants, and Israel Rubinstein. Purified ACE attenuates smokeless tobacco-induced increase in macromolecular efflux from the oral mucosa. J. Appl. Physiol. 83(1): 74–81, 1997.—The purpose of this study was to determine whether purified angiotensin I-converting enzyme (ACE) attenuates smokeless tobacco extract (STE)-induced increase in macromolecular efflux from the in situ oral mucosa. By using intravital microscopy, we found that suffusion of an aqueous extract of smokeless tobacco elicited significant concentration-dependent leaky site formation and increase in clearance of fluorescein isothiocyanate-labeled dextran (mol mass, 70 kDa) from the hamster cheek pouch ( P< 0.05). Suffusion of purified rabbit lung ACE significantly attenuated these responses in a concentration-dependent fashion ( P < 0.05). These effects were specific because purified ACE also significantly attenuated the increase in macromolecular efflux elicited by bradykinin, which is produced in the cheek pouch during suffusion of STE, but did not attenuate the increase elicted by adenosine. Moreover, suffusion of heat-inactivated purified ACE and purified superoxide dismutase had no significant effects on STE- and bradykinin-induced responses. Collectively, these data suggest that exogenous ACE attenuates STE-induced increase in macromolecular efflux from the in situ oral mucosa, in part, by promoting local bradykinin catabolism.

Smokeless tobacco-exposed oral keratinocytes increase macromolecular efflux from the in situ oral mucosa

1998 ◽  
Vol 274 (1) ◽  
pp. R104-R111 ◽  
Author(s):  
Israel Rubinstein ◽  
Xiao-Pei Gao ◽  
Sergei Pakhlevaniants ◽  
Dolphine Oda
Keyword(s):  
Oral Mucosa ◽  
Smokeless Tobacco ◽  
Fluorescein Isothiocyanate ◽  
Cheek Pouch ◽  
Oral Keratinocytes ◽  
Hamster Cheek Pouch ◽  
Hoe 140 ◽  
Significant Concentration

The purpose of this study was to determine whether supernatants of cultured human oral keratinocytes (HOK) exposed to an aqueous extract of smokeless tobacco (STE) increase macromolecular efflux from the oral mucosa in vivo and, if so, whether bradykinin mediates in part this response. Subconfluent monolayers of HOK were incubated with STE or media, and supernatants were collected 24, 48, and 72 h thereafter. Using intravital microscopy, we found that suffusion of supernatants of STE- but not media-exposed HOK elicited significant concentration- and time-dependent increases in efflux of fluorescein isothiocyanate-labeled dextran (mol mass 70 kDa) from the in situ hamster cheek pouch ( P < 0.05). These effects were significantly attenuated by HOE-140 and NPC-17647 but not by des-Arg9,[Leu8]-bradykinin. Proteolytic activity was increased in supernatants of STE- but not media-exposed HOK. However, a mixture of leupeptin, Bestatin, anddl-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid had no significant effects on HOK supernatant-induced responses. Collectively, these data suggest that oral keratinocytes modulate smokeless tobacco-induced increase in macromolecular efflux from the in situ oral mucosa in part by elaborating proteases that may account for local bradykinin production.

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.

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.

Aqueous smokeless tobacco extract impairs endothelium-dependent vasodilation in the oral mucosa

1996 ◽  
Vol 81 (1) ◽  
pp. 225-231 ◽  
Author(s):  
H. Suzuki ◽  
X. P. Gao ◽  
C. O. Olopade ◽  
H. A. Jaffe ◽  
S. Pakhlevaniants ◽  
...  
Keyword(s):  
Oral Mucosa ◽  
Aqueous Extract ◽  
Smokeless Tobacco ◽  
Thromboxane A2 ◽  
Arachidonic Acid Metabolism ◽  
Cheek Pouch ◽  
H2 Receptor Antagonist ◽  
Hamster Cheek Pouch ◽  
Tobacco Extract

The purpose of this study was to determine whether an aqueous extract of smokeless tobacco (moist snuff) modulates vasomotor tone in the oral mucosa in situ and, if so, to determine the mechanisms that mediated these responses. Using intravital microscopy, we found that the extract had no significant effects on diameter of resistance (second-order) arterioles [44 +/- 5 (SD) microns] in the hamster cheek pouch. However, it significantly attenuated vasodilation elicited by two endothelium-dependent agonists, acetylcholine and bradykinin (P < 0.05). These effects were specific because smokeless tobacco extract had no significant effects on vasodilation elicited by nitroglycerin, an endothelium-independent agonist. Indomethacin, a cyclooxygenase inhibitor, and SQ-29548, a thromboxane A2/prostaglandin H2-receptor antagonist, abrogated the attenuating effects of smokeless tobacco extract on acetylcholine- and bradykinin-induced vasodilation. These data indicate that an aqueous extract of smokeless tobacco impairs endothelium-dependent vasodilation in the oral mucosa in situ in a specific fashion and that these effects are mediated, in part, by cyclooxygenase products of arachidonic acid metabolism that stimulate thromboxane A2/prostaglandin H2 receptors.

scholarly journals Methotrexate potentiates bradykinin-induced increase in macromolecular efflux from the hamster oral mucosa

1997 ◽  
Vol 273 (4) ◽  
pp. R1254-R1262 ◽  
Author(s):  
Xiao-Pei Gao ◽  
Israel Rubinstein
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Oral Mucosa ◽  
Biosynthetic Pathway ◽  
Fluorescein Isothiocyanate ◽  
Cheek Pouch ◽  
Site Formation ◽  
Induced Responses ◽  
Hamster Cheek Pouch

The purpose of this study was to determine whether methotrexate modulates bradykinin-induced increase in macromolecular efflux from the in situ oral mucosa and whether this response is mediated by thel-arginine/nitric oxide biosynthetic pathway. Using intravital microscopy, we found that suffusion of methotrexate alone onto the hamster cheek pouch had no significant effects on leaky site formation and increase in clearance of fluorescein isothiocyanate-labeled dextran (molecular mass, 70 kDa). However, methotrexate significantly potentiated bradykinin-induced responses ( P < 0.05). These effects were associated with significant increases in nitrites concentration and guanosine 3′,5′-cyclic monophosphate-like immunoreactivity in the suffusate and were abrogated by N G-nitro-l-arginine methyl ester (l-NAME) but not N G-nitro-d-arginine methyl ester (d-NAME).l-Arginine, but notd-arginine, abolishedl-NAME-induced responses. ZnCI2 and indomethacin had no significant effects on methotrexate-induced responses. Methotrexate had no significant effects on adenosine- and ionomycin-induced increases in macromolecular efflux. Collectively, these data indicate that methotrexate amplifies bradykinin-induced increase in macromolecular efflux from the in situ oral mucosa in a specific, receptor- andl-arginine/nitric oxide biosynthetic pathway-dependent fashion.

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.

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.

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.

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