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)
Dodam
J R
JR
Department of Anatomy, Physiological Sciences and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh 27606, USA.
Olson
N C
NC
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000758:Anesthesia; D000818:Animals; D001965:Bromides / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D015237:Dinoprost / Q000097:blood; D015777:Eicosanoids / Q000378:metabolism*; D005459:Fluorides / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects*; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000033:anatomy & histology / Q000187:drug effects*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D011652:Pulmonary Circulation / Q000187:drug effects; D012129:Respiratory Function Tests; D017670:Sodium Compounds / Q000494:pharmacology; D013552:Swine; D013929:Thromboxane B2 / Q000097:blood / Q000378:metabolism
D001965:Bromides; D015777:Eicosanoids; D017670:Sodium Compounds; D000001:Calcimycin; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D015237:Dinoprost; D019204:GTP-Binding Proteins; C027938:sodium bromide; D005459:Fluorides; D007213:Indomethacin