Platelet-activating factor modulates microvascular dynamics through phospholipase C in the hamster cheek pouch.
We studied the interactions between platelet-activating factor (PAF) and phospholipase C (PLC) in the modulation of microvascular responses in the hamster cheek pouch using intravital microscopy and computer-assisted image analysis. Changes in arteriolar diameter and in integrated optical intensity (IOI, an index of vascular permeability) were measured. Fluorescein-isothiocyanate-labeled dextran 150 (FITC-Dx 150) served as a tracer for macromolecular transport. 2-Nitro-4-carboxyphenyl N,N-diphenylcarbamate (NCDC) and 1-(6-((17beta-3-methoxyestra-1,3, 5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5,-dione (U-73122), two PLC inhibitors, were applied topically in separate experiments. PAF at 10(-7) M elevated IOI from baseline to a mean +/- SEM value of 70. 7 +/- 8.9 units. Pretreatment with 10(-4) and 10(-5) M NCDC and with U-73122 at 10(-5) and 10(-6) M attenuated the maximal increment in mean IOI (+/-SEM) induced by PAF at 10(-7) M to mean +/- SEM values of 30.6 +/- 6.5, 39.3 +/- 6.0, 12.1 +/- 4.8, and 41.5 +/- 6.0, respectively. The simultaneous vasoconstrictor action of 10(-7) M PAF was expressed as the experimental-to-baseline ratio, with the baseline diameter adjusted to a value of 1. PAF constricted the arterioles to a mean +/- SEM ratio of 0.30 +/- 0.07. Pretreatment with the PLC inhibitors NCDC at 10(-4) and 10(-5) M NCDC and with U-73122 at 10(-5) and 10(-6) M attenuated 10(-7) M PAF-induced vasoconstriction to mean +/- SEM diameter ratios of 0.55 +/- 0.05, 0. 48 +/- 0.06, 0.55 +/- 0.08, and 0.58 +/- 0.06, respectively. Our results demonstrate that PLC is an element of the biochemical pathway involved in PAF modulation of microvascular permeability and in PAF modulation of arteriolar diameter.
Kim
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Program in Vascular Biology, UMDNJ-New Jersey Medical School, Newark, New Jersey, 07103-2714, USA.
Ramírez
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Durán
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D000287:Administration, Topical; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D001692:Biological Transport / Q000187:drug effects; D002219:Carbamates / Q000008:administration & dosage; D002610:Cheek / Q000098:blood supply*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004963:Estrenes / Q000008:administration & dosage; D008297:Male; D008647:Mesocricetus; D008833:Microcirculation / Q000187:drug effects / Q000201:enzymology*; D010539:Permeability; D048448:Phenylcarbamates; D010740:Phospholipases / Q000037:antagonists & inhibitors; D010972:Platelet Activating Factor / Q000378:metabolism* / Q000494:pharmacology; D011760:Pyrrolidinones / Q000008:administration & dosage; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects
D002219:Carbamates; D004963:Estrenes; D048448:Phenylcarbamates; D010972:Platelet Activating Factor; D011760:Pyrrolidinones; C025508:2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D010740:Phospholipases; D010738:Type C Phospholipases