Role of nitric oxide in leukotriene C4-induced increases in microvascular transport

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Abstract

The goal of this study was to determine the role of nitric oxide in alterations in macromolecular transport of the hamster cheek pouch in vivo in response to leukotriene C4. We used intravital fluorescent microscopy to examine the transport of macromolecules across the hamster cheek pouch in response to leukotriene C4 before and after application of an enzymatic inhibitor of nitric oxide, N(G)-monomethyl-L-arginine (L-NMMA; 1.0 μM). Increases in transport of macromolecules across the hamster cheek pouch were quantitated by the formation of venular leaky sites and clearance of fluorescein isothiocyanate-dextran (FITC-dextran; mol wt = 70 K). Leukotriene C4 (1.0 and 3.0 nM) produced an increase in the number of venular leaky sites and clearance of FITC-dextran-70K. Superfusion of L-NMMA (1.0 μM) significantly decreased leukotriene C4-induced increases in venular leaky sites and clearance of FITC-dextran-70K. In addition, superfusion of LY- 83583 (10 μM) significantly decreased leukotriene C4-induced increases in venular leaky sites. In contrast, superfusion of N(G)-monomethyl-D-arginine (D-NMMA; 1.0 μM), indomethacin (10 mg/kg iv), or diphenhydramine hydrochloride; 15-20 mg/kg iv) did not significantly alter leukotriene C4- induced increases in venular leaky sites. Thus these findings suggest that production of nitric oxide and subsequent activation of guanylate cyclase play an important role in formation of venular leaky sites and clearance of FITC-dextran-70K in response to application of leukotriene C4.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume265
Issue number1 34-1
StatePublished - Jan 1 1993

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Leukotriene C4
Nitric Oxide
omega-N-Methylarginine
Cheek
Cricetinae
6-anilino-5,8-quinolinedione
Diphenhydramine
Guanylate Cyclase
Indomethacin
Arginine
fluorescein isothiocyanate dextran

Keywords

  • N(G)-monomethyl-L-arginine
  • hamster cheek pouch
  • venular leaky sites

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

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title = "Role of nitric oxide in leukotriene C4-induced increases in microvascular transport",
abstract = "The goal of this study was to determine the role of nitric oxide in alterations in macromolecular transport of the hamster cheek pouch in vivo in response to leukotriene C4. We used intravital fluorescent microscopy to examine the transport of macromolecules across the hamster cheek pouch in response to leukotriene C4 before and after application of an enzymatic inhibitor of nitric oxide, N(G)-monomethyl-L-arginine (L-NMMA; 1.0 μM). Increases in transport of macromolecules across the hamster cheek pouch were quantitated by the formation of venular leaky sites and clearance of fluorescein isothiocyanate-dextran (FITC-dextran; mol wt = 70 K). Leukotriene C4 (1.0 and 3.0 nM) produced an increase in the number of venular leaky sites and clearance of FITC-dextran-70K. Superfusion of L-NMMA (1.0 μM) significantly decreased leukotriene C4-induced increases in venular leaky sites and clearance of FITC-dextran-70K. In addition, superfusion of LY- 83583 (10 μM) significantly decreased leukotriene C4-induced increases in venular leaky sites. In contrast, superfusion of N(G)-monomethyl-D-arginine (D-NMMA; 1.0 μM), indomethacin (10 mg/kg iv), or diphenhydramine hydrochloride; 15-20 mg/kg iv) did not significantly alter leukotriene C4- induced increases in venular leaky sites. Thus these findings suggest that production of nitric oxide and subsequent activation of guanylate cyclase play an important role in formation of venular leaky sites and clearance of FITC-dextran-70K in response to application of leukotriene C4.",
keywords = "N(G)-monomethyl-L-arginine, hamster cheek pouch, venular leaky sites",
author = "William Mayhan",
year = "1993",
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T1 - Role of nitric oxide in leukotriene C4-induced increases in microvascular transport

AU - Mayhan, William

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N2 - The goal of this study was to determine the role of nitric oxide in alterations in macromolecular transport of the hamster cheek pouch in vivo in response to leukotriene C4. We used intravital fluorescent microscopy to examine the transport of macromolecules across the hamster cheek pouch in response to leukotriene C4 before and after application of an enzymatic inhibitor of nitric oxide, N(G)-monomethyl-L-arginine (L-NMMA; 1.0 μM). Increases in transport of macromolecules across the hamster cheek pouch were quantitated by the formation of venular leaky sites and clearance of fluorescein isothiocyanate-dextran (FITC-dextran; mol wt = 70 K). Leukotriene C4 (1.0 and 3.0 nM) produced an increase in the number of venular leaky sites and clearance of FITC-dextran-70K. Superfusion of L-NMMA (1.0 μM) significantly decreased leukotriene C4-induced increases in venular leaky sites and clearance of FITC-dextran-70K. In addition, superfusion of LY- 83583 (10 μM) significantly decreased leukotriene C4-induced increases in venular leaky sites. In contrast, superfusion of N(G)-monomethyl-D-arginine (D-NMMA; 1.0 μM), indomethacin (10 mg/kg iv), or diphenhydramine hydrochloride; 15-20 mg/kg iv) did not significantly alter leukotriene C4- induced increases in venular leaky sites. Thus these findings suggest that production of nitric oxide and subsequent activation of guanylate cyclase play an important role in formation of venular leaky sites and clearance of FITC-dextran-70K in response to application of leukotriene C4.

AB - The goal of this study was to determine the role of nitric oxide in alterations in macromolecular transport of the hamster cheek pouch in vivo in response to leukotriene C4. We used intravital fluorescent microscopy to examine the transport of macromolecules across the hamster cheek pouch in response to leukotriene C4 before and after application of an enzymatic inhibitor of nitric oxide, N(G)-monomethyl-L-arginine (L-NMMA; 1.0 μM). Increases in transport of macromolecules across the hamster cheek pouch were quantitated by the formation of venular leaky sites and clearance of fluorescein isothiocyanate-dextran (FITC-dextran; mol wt = 70 K). Leukotriene C4 (1.0 and 3.0 nM) produced an increase in the number of venular leaky sites and clearance of FITC-dextran-70K. Superfusion of L-NMMA (1.0 μM) significantly decreased leukotriene C4-induced increases in venular leaky sites and clearance of FITC-dextran-70K. In addition, superfusion of LY- 83583 (10 μM) significantly decreased leukotriene C4-induced increases in venular leaky sites. In contrast, superfusion of N(G)-monomethyl-D-arginine (D-NMMA; 1.0 μM), indomethacin (10 mg/kg iv), or diphenhydramine hydrochloride; 15-20 mg/kg iv) did not significantly alter leukotriene C4- induced increases in venular leaky sites. Thus these findings suggest that production of nitric oxide and subsequent activation of guanylate cyclase play an important role in formation of venular leaky sites and clearance of FITC-dextran-70K in response to application of leukotriene C4.

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