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 |
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Sprache: | eng |
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Zusammenfassung: | 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. |
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ISSN: | 0014-2999 1879-0712 |
DOI: | 10.1016/S0014-2999(00)00632-4 |