Role of leukotriene C4 in pulmonary hypertension: platelet-activating factor vs. hypoxia.
The aim of this study was to determine whether leukotriene C4 (LTC4) is a mediator of hypoxic pulmonary vasoconstriction. We hypothesized that similar increases in LTC4, detected in the lung parenchyma and pulmonary vascular compartment during cyclooxygenase blockade with indomethacin (INDO), would be observed during an equal increase in pulmonary arterial pressure caused by acute alveolar hypoxia (HYP, 100% N2) or platelet-activating factor (PAF, 10 micrograms into the pulmonary artery). Rat lungs were perfused at constant flow in vitro with an albumin-Krebs-Henseleit solution. Mean pulmonary arterial pressure (n = 6 per group) increased from a base line of 10.9 +/- 1.2 to 15.8 +/- 2.1 (HYP + INDO) and 15.5 +/- 1.9 (SE) Torr (PAF + INDO). LTC4 levels increased only in response to PAF + INDO; perfusate levels increased from 0.4 +/- 0.07 to 5.3 +/- 1.1 ng/40 ml, and lung parenchymal levels increased from 1.9 +/- 0.07 to 22.8 +/- 5.3 ng/lung. Diethylcarbamazine (lipoxygenase inhibitor) reduced PAF-induced lung parenchymal levels of LTC4 by 68% and pulmonary hypertension by 63%. We conclude that 1) LTC4 is not a mediator of hypoxic pulmonary vasoconstriction and 2) intravascular PAF is a potent stimulus for LTC4 production in the lung parenchyma.
Davidson
D
D
Department of Pediatrics, Schneider Children's Hospital, Long Island Jewish Medical Center, Albert Einstein College of Medicine, New Hyde Park 11042.
Singh
M
M
Wallace
G F
GF
D000818:Animals; D016861:Cyclooxygenase Inhibitors; D006976:Hypertension, Pulmonary / Q000209:etiology* / Q000378:metabolism; D000860:Hypoxia / Q000150:complications*; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D010972:Platelet Activating Factor; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000378:metabolism*
D016861:Cyclooxygenase Inhibitors; D010972:Platelet Activating Factor; D013189:SRS-A; D007213:Indomethacin