Journal of Applied Physiology, Vol 58, Issue 3 710-716, Copyright © 1985 by American Physiological Society
Thromboxane synthase inhibition and perinatal pulmonary response to arachidonic acid
M. L. Tod and S. Cassin
Arachidonic acid causes dose-dependent increases in pulmonary vascular
resistance in perinatal lambs. The specific metabolites that produce this
effect are not known; however, a role for thromboxanes (TX's), potent
constrictors of vascular smooth muscle, has been proposed. The effects of a
specific inhibitor of TX synthase, OKY-1581, were tested in newborn and
ventilated fetal lambs using an in situ pump-perfused lower left lobe
preparation. Pulmonary and systemic responses of newborns and ventilated
fetuses to infusions of arachidonic acid were evaluated in the presence and
absence of OKY-1581. Increases in pulmonary vascular resistance caused by
arachidonic acid were diminished by TX synthase inhibition. The degree of
systemic hypotension observed with arachidonic acid infusions was
significantly greater in animals receiving OKY-1581 than in animals without
the inhibitor. The effect of OKY-1581 on periods of hypoxia was also
evaluated in newborn lambs. There were no significant differences in the
hypoxic pressor response in lambs with and without TX synthase inhibition.
These results suggest that OKY-1581 can reduce most of the pulmonary
vasoconstriction produced by arachidonic acid in perinatal lambs.
