AJP - Heart and Circulatory Physiology, Vol 254, Issue 1 120-H125, Copyright © 1988 by American Physiological Society
Specificity of FPL 57231 for leukotriene D4 receptors in fetal pulmonary circulation
G. E. Gause, R. Baker and S. Cassin
Department of Physiology, College of Medicine, University of Florida, Gainesville 32610.
The effects of leukotriene D4 and the putative leukotriene receptor
antagonist FPL 57231 were studied on the pulmonary circulation of
alpha-chloralose-anesthetized fetal lambs close to term. At constant
pulmonary inflow leukotriene D4 (LTD4, 0.1-10 micrograms), as bolus
injections, caused dose-dependent increases in pulmonary vascular
resistance. FPL 57231 (1.0-10 mg/kg) not only blocked the pressor responses
to LTD4 but also lowered the normal pulmonary vascular resistance in a
dose-dependent fashion. However, FPL 57231 also decreased the pulmonary
pressor response to U 46619, a thromboxane A2 mimic, as well as the pressor
response to phenylephrine HCl. Furthermore, the pressor responses to LTD4
were markedly reduced by cyclooxygenase inhibition. In preliminary
experiments we demonstrated that the phenidone derivative, BW755C, which is
a dual inhibitor of both cyclooxygenase and 5-lipoxygenase enzymes, did not
block the pressor response to hypoxia. We conclude that FPL 57231 decreases
fetal pulmonary vascular resistance by nonspecific mechanisms. Also the
action of LTD4, is indirect and by way of the cyclooxygenase system.
Although exogenous leukotrienes are able to produce a marked pulmonary
pressor response, endogenous leukotrienes are probably not responsible for
the hypoxic pulmonary pressor response of the fetal lung or its normally
high pulmonary vascular resistance.
