Importance of vasoconstriction in lipid mediator-induced pulmonary edema.
Lipid mediators of inflammation cause pulmonary edema, yet it is unclear to what degree hemodynamic alterations or increased vascular permeability contribute to lung edema formation. The isolated rat lung preparation was used to examine the effect of leukotriene C4 (LTC4) and platelet-activating factor (PAF) on pulmonary arterial pressure (Ppa), lung microvascular pressure (Pmv), lung wet-to-dry weight ratio, and the 125I-albumin escape index. We first defined the response of the isolated rat lung perfused with protein-free salt solution to hydrodynamic stress by raising the lung outflow pressure. Sustained elevation of the lung outflow pressure less than 5.5 cmH2O (4.01 mmHg) caused a negligible increase in Ppa and wet-to-dry lung weight ratio. Elevation of outflow pressures greater than 7.5 cmH2O (5.4 mmHg) increased the vascular albumin escape index more than the lung wet-to-dry weight ratio. Dibutyryl adenosine 3',5'-cyclic monophosphate (db-cAMP) inhibited the increase in albumin escape index because of increased lung outflow pressure, suggesting perhaps a pressure-independent microvascular membrane effect of db-cAMP. Both LTC4 (2-micrograms bolus) and PAF (2-2,000 ng/ml perfusate) increased the albumin escape index in association with increases in Ppa and Pmv. Because the increased albumin escape index after LTC4 or PAF injection was largely accounted for by the increased vascular pressures and because db-cAMP and papaverine inhibited the rise in vascular pressures and in the albumin escape index, we conclude that vasoconstriction is an important contributor to LTC4- and PAF-induced edema formation in rat lungs.
Sakai
A
A
Cardiovascular Pulmonary Research Laboratory, University of Colorado Health Sciences Center, Denver 80262.
Chang
S W
SW
Voelkel
N F
NF
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D066298:In Vitro Techniques; D008168:Lung / Q000098:blood supply* / Q000503:physiopathology; D008297:Male; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011654:Pulmonary Edema / Q000139:chemically induced* / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
D010972:Platelet Activating Factor; D013189:SRS-A