Journal of Applied Physiology, Vol 78, Issue 2 569-577, Copyright © 1995 by American Physiological Society
Effect of fluoride on cardiopulmonary function and release of eicosanoids in pigs
J. R. Dodam and N. C. Olson
Department of Anatomy, Physiological Sciences and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh 27606, USA.
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)
