Aa. Noel et al., PLATELET-ACTIVATING-FACTOR AND NITRIC-OXIDE MEDIATE MICROVASCULAR PERMEABILITY IN ISCHEMIA-REPERFUSION INJURY, Microvascular research, 52(3), 1996, pp. 210-220
Increased microvascular permeability is a hallmark of ischemia-reperfu
sion (I/R) injury. We hypothesized that platelet-activating factor (PA
F) and nitric oxide (NO) are involved in the extravasation of macromol
ecules in YR injury. To block endogenous PAF, we used a PAF-receptor a
ntagonist (WEB 2086; 2 mg/kg, i.v). To inhibit endogenous nitric oxide
, we employed L-N-G-monomethyl arginine (10(-5) M L-NMMA), a NO syntha
se inhibitor. We assessed microvascular permeability to FITC-dextran 1
50 by measuring changes in integrated optical intensity (Delta IOI) us
ing computer-assisted image analysis in the hamster cheek pouch. We ex
amined one area of isehemia and one control area in each pouch. Ischem
ia was induced for 2 hr and was followed by 1 hr of reperfusion. Six g
roups were investigated. Group 1 (n = 5) had no pharmacologic interven
tion; Group 2 (n = 5) received WEB 2086 15 min before reperfusion; Gro
up 3 (n = 5) received WEB 2086 at reperfusion; Group LC (II = 5), WEB
2086 was infused 15 min after the onset of reperfusion. Group 5 (n = 3
) received topical L-NMMA (30 min prior to reperfusion and continuousl
y for the remainder of the experiment). Group 6 (n = 3) received both
L-NMMA (as in Group 5) and WEB 2086 (administered 15 min after reperfu
sion). In Group 1, YR increased the mean (+/-SEM) Delta IOI value from
61.5 +/- 11.1 to 127.2 +/- 26.1. WEB 2086 inhibited the increase in D
elta IOI at each time point. Similarly, the groups given L-NMMA alone
and L-NMMA + WEB 2086 showed no difference between ischemic and contro
l groups. Our data demonstrate that (1) PAF and nitric oxide are invol
ved in the permeability changes associated with the microvascular dysf
unction of ischemia-reperfusion injury; (2) inhibitors of PAF and nitr
ic oxide synthase are effective in attenuating macromolecular extravas
ation when given during ischemia or after initiation of reperfusion. (
C) 1996 Academic Press. Inc.