Obligatory role of nitric oxide in platelet-activating factor-induced microvascular leakage

We examined the independent and interdependent effects of platelet-activating factor (PAF) and nitric oxide (NO) on microvascular leakage of fluorescein isothiocyanate (FITC)-dextran in the cheek pouch microcirculation of anesthetized hamsters. Superfusing the cheek pouch microcirculation with 100-n...

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Veröffentlicht in:European journal of pharmacology 2000-09, Vol.404 (3), p.387-394
Hauptverfasser: Klabunde, Richard E, Anderson, Denise E
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description We examined the independent and interdependent effects of platelet-activating factor (PAF) and nitric oxide (NO) on microvascular leakage of fluorescein isothiocyanate (FITC)-dextran in the cheek pouch microcirculation of anesthetized hamsters. Superfusing the cheek pouch microcirculation with 100-nM PAF elicited rapid leakage of FITC-dextran that was markedly inhibited by prior treatment with a nitric oxide synthase (NOS) inhibitor, N ω-nitro- l-arginine ( l-NA; 1 μM). This inhibition by l-NA was completely reversed by application of a NO donor ( S-nitroso- N-acetylpenicillamine, SNAP; 10 μM) at the same time PAF was applied. SNAP alone, however, did not cause leakage of FITC-dextran; neither did it enhance PAF-induced leakage. PAF-induced leakage was completely inhibited by prior treatment with the guanylyl cyclase inhibitor 1 H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 μM). 8-bromoguanosine 3′,5′-cyclic monophosphate (8-br-cGMP) did not reverse this inhibition by ODQ although this cell permeable cGMP analog was able to completely reverse arteriolar vasoconstriction produced by ODQ. These results indicate that PAF-induced leakage of FITC-dextran in the hamster cheek pouch microcirculation requires an intact NO/cGMP pathway, although NO production does not cause PAF-induced leakage. This supports the hypothesis that NO plays an obligatory role in PAF-induced leakage.
doi_str_mv 10.1016/S0014-2999(00)00632-4
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Superfusing the cheek pouch microcirculation with 100-nM PAF elicited rapid leakage of FITC-dextran that was markedly inhibited by prior treatment with a nitric oxide synthase (NOS) inhibitor, N ω-nitro- l-arginine ( l-NA; 1 μM). This inhibition by l-NA was completely reversed by application of a NO donor ( S-nitroso- N-acetylpenicillamine, SNAP; 10 μM) at the same time PAF was applied. SNAP alone, however, did not cause leakage of FITC-dextran; neither did it enhance PAF-induced leakage. PAF-induced leakage was completely inhibited by prior treatment with the guanylyl cyclase inhibitor 1 H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 μM). 8-bromoguanosine 3′,5′-cyclic monophosphate (8-br-cGMP) did not reverse this inhibition by ODQ although this cell permeable cGMP analog was able to completely reverse arteriolar vasoconstriction produced by ODQ. These results indicate that PAF-induced leakage of FITC-dextran in the hamster cheek pouch microcirculation requires an intact NO/cGMP pathway, although NO production does not cause PAF-induced leakage. This supports the hypothesis that NO plays an obligatory role in PAF-induced leakage.</description><subject>Animals</subject><subject>Arteriole</subject><subject>Biological and medical sciences</subject><subject>Blood vessels and receptors</subject><subject>Capillary Permeability - drug effects</subject><subject>Capillary Permeability - physiology</subject><subject>Cheek - blood supply</subject><subject>Cricetinae</subject><subject>Dextrans - pharmacokinetics</subject><subject>FITC-dextran</subject><subject>Fluorescein-5-isothiocyanate - analogs &amp; derivatives</subject><subject>Fluorescein-5-isothiocyanate - pharmacokinetics</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Male</subject><subject>Mesocricetus</subject><subject>Microcirculation</subject><subject>Nitric oxide (NO)</subject><subject>Nitric Oxide - pharmacology</subject><subject>Nitric Oxide Donors - pharmacology</subject><subject>Nitric oxide synthase (NOS) inhibitor</subject><subject>Nitric Oxide Synthase - antagonists &amp; inhibitors</subject><subject>Nitric Oxide Synthase - metabolism</subject><subject>Penicillamine - analogs &amp; derivatives</subject><subject>Penicillamine - pharmacology</subject><subject>Permeability</subject><subject>Platelet Activating Factor - pharmacology</subject><subject>Platelet-activating factor (PAF)</subject><subject>Vasoconstriction - drug effects</subject><subject>Vasoconstriction - physiology</subject><subject>Vasodilator Agents - pharmacology</subject><subject>Vertebrates: cardiovascular system</subject><issn>0014-2999</issn><issn>1879-0712</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1PVDEUhhsikRH9CZgujNHF1dPer3ZFDAEkIWGhrlw0nfZ0UuncDm3vBP69hZkoO1bnLJ73nDcPIScMvjBgw9cfAKxruJTyE8BngKHlTXdAFkyMsoGR8Vdk8Q85Im9y_gMAveT9a3LEQMphgG5Bft8sg1_pEtMDTTEgjY5OviRvaLz3Fqmf6CboggFLo03xW138tKKu7jE1frKzQUvX3qS41dnMQScaUN_qFb4lh06HjO_285j8ujj_efa9ub65vDr7dt2YVkJpWjEao4UTojfajoaNThiJ1jrBmO3aETRnA-sR3XKpucDeghmkYVYKN3SuPSYfd3c3Kd7NmIta-2wwBD1hnLMaORet6GQF-x1Yy-ac0KlN8mudHhQD9WhVPVlVj8oUgHqyqrqae79_MC_XaJ-ldhor8GEPVAU6uKQn4_N_rpMjH_qKne4wrDa2HpPKxuNUBfqEpigb_QtN_gJAhJWz</recordid><startdate>20000922</startdate><enddate>20000922</enddate><creator>Klabunde, Richard E</creator><creator>Anderson, Denise E</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20000922</creationdate><title>Obligatory role of nitric oxide in platelet-activating factor-induced microvascular leakage</title><author>Klabunde, Richard E ; Anderson, Denise E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c390t-387cca8f885cad7c17f8c9eddf811d4370a21615eefbba28e5d0c69c1d98f64f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Animals</topic><topic>Arteriole</topic><topic>Biological and medical sciences</topic><topic>Blood vessels and receptors</topic><topic>Capillary Permeability - drug effects</topic><topic>Capillary Permeability - physiology</topic><topic>Cheek - blood supply</topic><topic>Cricetinae</topic><topic>Dextrans - pharmacokinetics</topic><topic>FITC-dextran</topic><topic>Fluorescein-5-isothiocyanate - analogs &amp; derivatives</topic><topic>Fluorescein-5-isothiocyanate - pharmacokinetics</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Male</topic><topic>Mesocricetus</topic><topic>Microcirculation</topic><topic>Nitric oxide (NO)</topic><topic>Nitric Oxide - pharmacology</topic><topic>Nitric Oxide Donors - pharmacology</topic><topic>Nitric oxide synthase (NOS) inhibitor</topic><topic>Nitric Oxide Synthase - antagonists &amp; inhibitors</topic><topic>Nitric Oxide Synthase - metabolism</topic><topic>Penicillamine - analogs &amp; derivatives</topic><topic>Penicillamine - pharmacology</topic><topic>Permeability</topic><topic>Platelet Activating Factor - pharmacology</topic><topic>Platelet-activating factor (PAF)</topic><topic>Vasoconstriction - drug effects</topic><topic>Vasoconstriction - physiology</topic><topic>Vasodilator Agents - pharmacology</topic><topic>Vertebrates: cardiovascular system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Klabunde, Richard E</creatorcontrib><creatorcontrib>Anderson, Denise E</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Klabunde, Richard E</au><au>Anderson, Denise E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Obligatory role of nitric oxide in platelet-activating factor-induced microvascular leakage</atitle><jtitle>European journal of pharmacology</jtitle><addtitle>Eur J Pharmacol</addtitle><date>2000-09-22</date><risdate>2000</risdate><volume>404</volume><issue>3</issue><spage>387</spage><epage>394</epage><pages>387-394</pages><issn>0014-2999</issn><eissn>1879-0712</eissn><coden>EJPHAZ</coden><abstract>We examined the independent and interdependent effects of platelet-activating factor (PAF) and nitric oxide (NO) on microvascular leakage of fluorescein isothiocyanate (FITC)-dextran in the cheek pouch microcirculation of anesthetized hamsters. Superfusing the cheek pouch microcirculation with 100-nM PAF elicited rapid leakage of FITC-dextran that was markedly inhibited by prior treatment with a nitric oxide synthase (NOS) inhibitor, N ω-nitro- l-arginine ( l-NA; 1 μM). This inhibition by l-NA was completely reversed by application of a NO donor ( S-nitroso- N-acetylpenicillamine, SNAP; 10 μM) at the same time PAF was applied. SNAP alone, however, did not cause leakage of FITC-dextran; neither did it enhance PAF-induced leakage. PAF-induced leakage was completely inhibited by prior treatment with the guanylyl cyclase inhibitor 1 H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 μM). 8-bromoguanosine 3′,5′-cyclic monophosphate (8-br-cGMP) did not reverse this inhibition by ODQ although this cell permeable cGMP analog was able to completely reverse arteriolar vasoconstriction produced by ODQ. These results indicate that PAF-induced leakage of FITC-dextran in the hamster cheek pouch microcirculation requires an intact NO/cGMP pathway, although NO production does not cause PAF-induced leakage. This supports the hypothesis that NO plays an obligatory role in PAF-induced leakage.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>10996604</pmid><doi>10.1016/S0014-2999(00)00632-4</doi><tpages>8</tpages></addata></record>
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subjects Animals
Arteriole
Biological and medical sciences
Blood vessels and receptors
Capillary Permeability - drug effects
Capillary Permeability - physiology
Cheek - blood supply
Cricetinae
Dextrans - pharmacokinetics
FITC-dextran
Fluorescein-5-isothiocyanate - analogs & derivatives
Fluorescein-5-isothiocyanate - pharmacokinetics
Fundamental and applied biological sciences. Psychology
Male
Mesocricetus
Microcirculation
Nitric oxide (NO)
Nitric Oxide - pharmacology
Nitric Oxide Donors - pharmacology
Nitric oxide synthase (NOS) inhibitor
Nitric Oxide Synthase - antagonists & inhibitors
Nitric Oxide Synthase - metabolism
Penicillamine - analogs & derivatives
Penicillamine - pharmacology
Permeability
Platelet Activating Factor - pharmacology
Platelet-activating factor (PAF)
Vasoconstriction - drug effects
Vasoconstriction - physiology
Vasodilator Agents - pharmacology
Vertebrates: cardiovascular system
title Obligatory role of nitric oxide in platelet-activating factor-induced microvascular leakage
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