Dextran sulfate and heparin sulfate inhibit platelet-activating factor-induced pulmonary edema.
We tested the hypothesis that dextran sulfate and heparin sulfate inhibit platelet-activating factor- (PAF) induced pulmonary edema in the isolated perfused guinea pig lung via a charge-dependent mechanism. Dextran sulfate prevented the changes in pulmonary capillary pressure (Ppc, 7.8 +/- 0.9 vs. 14.0 +/- 0.7 cmH2O), lung weight gain (dW, +0.48 +/- 0.29 vs. +8.41 +/- 2.07 g), and pulmonary edema formation or wet-to-dry weight ratio [(W-D)/D, 6.5 +/- 0.3 vs. 13.2 +/- 2.6] occurring 60 min after PAF infusion (10(-11) M) into an isolated lung. The unsulfated form of dextran had no protective effect [Ppc, dW, and (W-D)/D, 11.9 +/- 1.4 cmH2O, +5.33 +/- 2.18 g, and 11.2 +/- 3.2, respectively]. The unrelated anionic compound, heparin sulfate, also inhibited the PAF response [Ppc, dW, and (W-D)/D, 7.0 +/- 0.5 cmH2O, +0.61 +/- 0.32 g, and 6.1 +/- 0.2, respectively], whereas the partially desulfated form of heparin was not effective in inhibiting PAF-induced edema [Ppc, dW, and (W-D)/D, 15.1 +/- 0.7 cmH2O, +6.07 +/- 1.58 g, and 10.0 +/- 1.2, respectively]. When the metachromatic dye crystal violet was used as an indicator of charge interactions, the sulfated compounds interacted with PAF in vitro. The data indicate that PAF-induced pulmonary edema is inhibited by sulfated polysaccharides, possibly via a charge interaction between negatively charged compounds and PAF.
Hocking
D
D
Research Service, Veterans Affairs Medical Center, Albany, New York.
Ferro
T J
TJ
Johnson
A
A
D000818:Animals; D016264:Dextran Sulfate / Q000378:metabolism / Q000494:pharmacology*; D004563:Electrochemistry; D006168:Guinea Pigs; D006439:Hemodynamics / Q000187:drug effects; D006493:Heparin / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D010477:Perfusion; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D011654:Pulmonary Edema / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D013431:Sulfates / Q000378:metabolism
D010972:Platelet Activating Factor; D013431:Sulfates; D006493:Heparin; D016264:Dextran Sulfate