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

  • Klabunde R
  • Anderson D
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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. (C) 2000 Elsevier Science B.V.

Author-supplied keywords

  • Arteriole
  • FITC-dextran
  • Microcirculation
  • Nitric oxide (NO)
  • Nitric oxide synthase (NOS) inhibitor
  • Permeability
  • Platelet-activating factor (PAF)

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  • Richard E. Klabunde

  • Denise E. Anderson

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