Effect of fluoride on cardiopulmonary function and release of eicosanoids in pigs

Fluoroaluminates are believed to stimulate guanine nucleotide-binding (G) proteins, leading to activation of effector enzymes and release of vasoactive mediators. As a model for G protein-induced cardiopulmonary dysfunction, we infused NaF (0.9 M in 0.9% NaCl at 15 microliters.kg-1.min-1 for 3 h i.v.) in the presence (n = 8) and absence (n = 4) of AlCl3 (0.6 microgram.kg-1.min-1) into pigs anesthetized with pentobarbital sodium. NaF, with or without AlCl3, induced progressive deterioration of cardiopulmonary function after 1 h of infusion. At 3 h, mean pulmonary arterial pressure, pulmonary vascular resistance (PVR), tracheal pressure, and plasma concentrations of thromboxane B2 (TxB2), 6-ketoprostaglandin F1 alpha, and prostaglandin F2 alpha were significantly (P < 0.05) increased to approximately 200, 520, 175, 759, 402, and 336%, respectively, of baseline values (0 h). At 3 h, cardiac index and arterial PO2 decreased 38% and 28 Torr, respectively, from baseline values. Although indomethacin blocked the NaF-induced increase in plasma TxB2 concentration, the cyclooxygenase inhibitor did not modify any cardiopulmonary parameter measured or calculated, except for a transient reduction in PVR at 2.5 h. In porcine whole blood treated with AlF4- (30 mM NaF + 10 microM AlCl3) in vitro for 0.5 h, TxB2 concentration increased to 649% of the control value. In porcine alveolar macrophages labeled with [3H]arachidonic acid, AlF4- (30 mM NaF + 10 microM AlCl3) induced release of radioactivity to 165, 539, and 573% of control values after 0.5, 1, and 2 h of incubation, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)