Cigarette smoke extract attenuates endothelium-dependent arteriolar dilatation in vivo

1991 ◽  
Vol 261 (6) ◽  
pp. H1913-H1918 ◽  
Author(s):  
I. Rubenstein ◽  
T. Yong ◽  
S. I. Rennard ◽  
W. G. Mayhan
Keyword(s):  
Cigarette Smoke ◽  
Intravital Microscopy ◽  
Cigarette Smoke Extract ◽  
Cheek Pouch ◽  
Hamster Cheek Pouch ◽  
Before And After ◽  
Baseline Diameter

The purpose of this study was to examine the effects of cigarette smoke extract on endothelium-dependent and endothelium-independent dilatation of arterioles in vivo. Using intravital microscopy, we measured diameter of arterioles contained within the microcirculation of the hamster cheek pouch during suffusion with acetylcholine and nitroglycerin, before and after treatment with cigarette smoke extract. Under control conditions, acetylcholine and nitroglycerin produced dose-related dilatation of cheek pouch arterioles. Superfusion of cigarette smoke extract (1.0%) did not alter baseline diameter of arterioles or vasodilatation in response to nitroglycerin but impaired dilatation of arterioles in response to acetylcholine. Next, we examined the possibility that impaired dilatation of cheek pouch arterioles in response to acetylcholine after exposure to cigarette smoke extract may be related to the release of substances produced via the cyclooxygenase pathway. In indomethacin-pretreated hamsters, acetylcholine produced similar vasodilatation before and after exposure to cigarette smoke extract. Thus these findings suggest that cigarette smoke extract impairs endothelium-dependent responses of cheek pouch arterioles. The mechanism of impaired responses of cheek pouch arterioles after exposure to cigarette smoke extract appears to be related to the release of substances produced via the cyclooxygenase pathway.

Effect of cigarette smoke extract on arteriolar dilatation in vivo

1996 ◽  
Vol 81 (5) ◽  
pp. 1996-2003 ◽  
Author(s):  
William G. Mayhan ◽  
Glenda M. Sharpe
Keyword(s):  
Potassium Channels ◽  
Adenylate Cyclase ◽  
Cigarette Smoke ◽  
Intravital Microscopy ◽  
Cigarette Smoke Extract ◽  
Cheek Pouch ◽  
Hamster Cheek Pouch ◽  
Baseline Diameter

Mayhan, William G., and Glenda M. Sharpe. Effect of cigarette smoke extract on arteriolar dilatation in vivo. J. Appl. Physiol. 81(5): 1996–2003, 1996.—The goal of this study was to determine whether cigarette smoke extract alters dilatation of arterioles in vivo in response to agonists that produce activation of ATP-sensitive potassium channels and activation of adenylate cyclase. By using intravital microscopy, we measured diameter of arterioles contained within the microcirculation of the hamster cheek pouch during suffusion with agonists in the absence and presence of cigarette smoke extract (0.1, 0.5, and 1.0%). Before treatment with cigarette smoke extract, activation of ATP-sensitive potassium channels with aprikalim and cromakalim produced dose-related dilatation of cheek pouch arterioles. Similarly, activation of adenylate cyclase with isoproterenol and forskolin produced dose-related dilatation of cheek pouch arterioles before treatment with cigarette smoke extract. Superfusion of 0.1% cigarette smoke extract did not change baseline diameter of arterioles and did not alter responses of cheek pouch arterioles to activation of ATP-sensitive potassium channels and adenylate cyclase. Superfusion of 0.5 and 1.0% cigarette smoke extract also did not alter baseline diameter of arterioles but did impair dilatation of arterioles in response to activation of ATP-sensitive potassium channels and adenylate cyclase. These findings suggest that cigarette smoke extract impairs dilatation of resistance arterioles in response to activation of important cellular dilator pathways.

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.

Neutral endopeptidase modulates substance P-induced vasodilation in vivo

1995 ◽  
Vol 78 (2) ◽  
pp. 562-568 ◽  
Author(s):  
X. P. Gao ◽  
I. Rubinstein
Keyword(s):  
Substance P ◽  
Oral Mucosa ◽  
Intravital Microscopy ◽  
Neutral Endopeptidase ◽  
Cheek Pouch ◽  
Induced Responses ◽  
Hamster Cheek Pouch ◽  
Arteriolar Diameter ◽  
Significant Concentration

The purpose of this study was to investigate whether neutral endopeptidase (NEP; EC 3.4.24.11) modulates substance P-induced vasodilation in the oral mucosa in vivo. Using intravital microscopy, we measured the diameter of second-order arterioles (44–70 microns) in the hamster cheek pouch during suffusion of capsaicin and substance P. We found that capsaicin (0.1 and 10.0 nM) induced significant concentration-dependent vasodilations (13 +/- 4 and 39 +/- 7% increase from baseline, respectively; P < 0.05) that were significantly potentiated by phosphoramidon (10.0 nM), a selective NEP inhibitor (35 +/- 15 and 61 +/- 12% increase from baseline, respectively; P < 0.05). Substance P (0.1 and 10.0 nM) also induced significant concentration-dependent vasodilations (7 +/- 3 and 25 +/- 8% increase from baseline, respectively; P < 0.05) that were mediated by the COOH-terminal of the molecule. Substance P-induced responses were significantly potentiated by phosphoramidon (34 +/- 9 and 53 +/- 10% increase from baseline, respectively; P < 0.05) and thiorphan (10.0 microM), a selective NEP inhibitor (44 +/- 11 and 53 +/- 10% increase from baseline, respectively; P < 0.05). Substance P-(1–9) had no significant effects on arteriolar diameter. Suffusion of captopril, leupeptin, Bestatin, and DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid together had no significant effects on substance P-induced vasodilation. Phosphoramidon did not potentiate nitroglycerin-induced vasodilation. These data indicate that NEP modulates substance P-induced vasodilation in the hamster cheek pouch in vivo. We suggest that any decrease in tissue NEP activity may amplify neurogenic vasodilation in the oral mucosa.

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.

Peptidases modulate bradykinin-induced arteriolar dilation in the hamster cheek pouch

1994 ◽  
Vol 266 (1) ◽  
pp. H93-H98 ◽  
Author(s):  
X. P. Gao ◽  
P. Anding ◽  
R. A. Robbins ◽  
S. I. Rennard ◽  
I. Rubinstein
Keyword(s):  
Proteinase Inhibitors ◽  
Neutral Endopeptidase ◽  
Cheek Pouch ◽  
Induced Responses ◽  
Hamster Cheek Pouch ◽  
Before And After ◽  
Peripheral Microcirculation ◽  
Membrane Bound ◽  
Arteriolar Diameter

The purpose of this study was to investigate whether angiotensin-converting enzyme (ACE; EC 3.4.15.1) and neutral endopeptidase (NEP; EC 3.4.24.11), two membrane-bound metalloenzymes that are widely distributed in the peripheral microcirculation and degrade kinins very effectively, modulate bradykinin-induced arteriolar dilation in vivo. Using intravital microscopy, we measured diameter of second-order arterioles in the hamster cheek pouch during suffusion of bradykinin (0.1–10.0 microM) before and after topical application of captopril (10.0 microM) and phosphoramidon (10.0 nM). We found that each inhibitor significantly potentiated bradykinin-induced increase in arteriolar diameter (P < 0.05). Suffusion of other proteinase inhibitors (excluding ACE and NEP inhibitors) had no significant effect on bradykinin-induced responses. Captopril and phosphoramidon did not potentiate isoproterenol (0.1 microM)-induced arteriolar dilation in the cheek pouch. Collectively, these data indicate that ACE and NEP each plays an important role in regulating bradykinin-induced vasorelaxation in the peripheral microcirculation in vivo.

Effect of nicotine on endothelium-dependent arteriolar dilatation in vivo

1997 ◽  
Vol 272 (5) ◽  
pp. H2337-H2342 ◽  
Author(s):  
W. G. Mayhan ◽  
K. P. Patel
Keyword(s):  
Vascular Disease ◽  
Peripheral Vascular Disease ◽  
Peripheral Resistance ◽  
Cheek Pouch ◽  
Peripheral Vascular ◽  
Hamster Cheek Pouch ◽  
Before And After ◽  
Primary Risk Factor ◽  
Selective Impairment

Smoking is a primary risk factor in coronary and peripheral vascular disease. However, the precise component of cigarette smoke that contributes to the pathogenesis of vascular disease remains unclear. The goal of this study was to determine the effect of nicotine on endothelium-dependent dilatation of peripheral resistance arterioles in vivo. We measured the diameter of resistance arterioles (approximately 50 microns in diameter) contained within the microcirculation of the hamster cheek pouch in response to endothelium-dependent (acetylcholine and ADP) and -independent (nitroglycerin) agonists before and after an intravenous infusion of vehicle or two concentrations of nicotine. Acetylcholine, ADP, and nitroglycerin produced a dose-related dilatation of the cheek pouch arterioles under control conditions. Endothelium-dependent, but not -independent, dilatation of arterioles was modestly impaired by an infusion of a low concentration of nicotine (1.0 microgram.kg-1.min-1). Infusion of a higher concentration of nicotine (2 micrograms.kg-1.min-1), which increased the plasma level of nicotine to 14 +/- 1.6 ng/ml, produced a profound selective impairment in endothelium-dependent vasodilatation. We suggest that elevations in plasma nicotine may contribute to the pathogenesis of the peripheral vascular disease observed in smokers.

Pirfenidone mediates cigarette smoke extract induced inflammation and oxidative stress in vitro and in vivo

2021 ◽  
Vol 96 ◽  
pp. 107593
Author(s):  
Yiming Ma ◽  
Lijuan Luo ◽  
Xiangming Liu ◽  
Herui Li ◽  
Zihang Zeng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cigarette Smoke ◽  
Cigarette Smoke Extract ◽  
And Oxidative Stress

scholarly journals Signaling via β2 Integrins Triggers Neutrophil-Dependent Alteration in Endothelial Barrier Function

2000 ◽  
Vol 191 (11) ◽  
pp. 1829-1840 ◽  
Author(s):  
Narinder Gautam ◽  
Heiko Herwald ◽  
Per Hedqvist ◽  
Lennart Lindbom
Keyword(s):  
Protein S ◽  
Endothelial Barrier ◽  
Cheek Pouch ◽  
Cross Linking ◽  
Endothelial Lining ◽  
Hamster Cheek Pouch ◽  
Cationic Protein ◽  
Edema Formation ◽  
Β2 Integrins

Activation of polymorphonuclear leukocytes (PMNs) and adhesion to the endothelial lining is a major cause of edema formation. Although known to be dependent on the function of β2 integrins (CD11/CD18), the precise mechanisms by which adherent PMNs may impair endothelial barrier capacity remain unclear. Here, the role of transmembrane signaling by β2 integrins in PMN-induced alterations in tight junctional permeability of cultured endothelial cell (EC) monolayers was investigated. PMN activation, in the absence of proinflammatory stimuli, was accomplished through antibody cross-linking of CD11b/CD18, mimicking adhesion-dependent receptor engagement. CD18 cross-linking in PMNs added to the EC monolayer provoked a prompt increase in EC permeability that coincided with a rise in EC cytosolic free Ca2+ and rearrangement of actin filaments, events similar to those evoked by chemoattractant PMN activation. Cell-free supernatant obtained after CD18 cross-linking in suspended PMNs triggered an EC response indistinguishable from that induced by direct PMN activation, and caused clear-cut venular plasma leakage when added to the hamster cheek pouch in vivo preparation. The PMN-evoked EC response was specific to β2 integrin engagement inasmuch as antibody cross-linking of l-selectin or CD44 was without effect on EC function. Our data demonstrate a causal link between outside-in signaling by β2 integrins and the capacity of PMNs to induce alterations in vascular permeability, and suggest a paracrine mechanism that involves PMN-derived cationic protein(s) in the cellular crosstalk between PMNs and ECs.

Capillaries demonstrate changes in membrane potential in response to pharmacological stimuli

1998 ◽  
Vol 274 (1) ◽  
pp. H60-H65 ◽  
Author(s):  
Eugene D. McGahren ◽  
James M. Beach ◽  
Brian R. Duling
Keyword(s):  
Endothelial Cells ◽  
Membrane Potential ◽  
Fluorescence Emission ◽  
Cheek Pouch ◽  
Surrounding Tissue ◽  
Hamster Cheek Pouch ◽  
Capillary Membrane ◽  
Resistance Vessels ◽  
Capillary Endothelial Cells

It has been proposed that capillaries can detect changes in tissue metabolites and generate signals that are communicated upstream to resistance vessels. The mechanism for this communication may involve changes in capillary endothelial cell membrane potentials which are then conducted to upstream arterioles. We have tested the capacity of capillary endothelial cells in vivo to respond to pharmacological stimuli. In a hamster cheek pouch preparation, capillary endothelial cells were labeled with the voltage-sensitive dye di-8-ANEPPS. Fluorescence from capillary segments (75–150 μm long) was excited at 475 nm and recorded at 560 and 620 nm with a dual-wavelength photomultiplier system. KCl was applied using pressure injection, and acetylcholine (ACh) and phenylephrine (PE) were applied iontophoretically to these capillaries. Changes in the ratio of the fluorescence emission at two emission wavelengths were used to estimate changes in the capillary endothelial membrane potential. Application of KCl resulted in depolarization, whereas application of the vehicle did not. Application of ACh and PE resulted in hyperpolarization and depolarization, respectively. The capillary responses could be blocked by including a receptor antagonist (atropine or prazosin, respectively) in the superfusate. We conclude that the capillary membrane potential is capable of responding to pharmacological stimuli. We hypothesize that capillaries can respond to changes in the milieu of surrounding tissue via changes in endothelial membrane potential.

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