Journal of Applied Physiology, Vol 62, Issue 1 129-133, Copyright © 1987 by American Physiological Society
Lipoxygenase and cyclooxygenase blockade by BW 755C enhances pulmonary hypoxic vasoconstriction
R. C. Garrett, S. Foster and H. M. Thomas 3rd
Lipoxygenase products (leukotrienes) have been proposed as the mediators of
pulmonary hypoxic vasoconstriction. However, the supporting data are
inconclusive because the lipoxygenase and leukotriene receptor blockers
that reduce hypoxic vasoconstriction (such as diethylcarbamazine and the
FPL's) have confounding effects. We investigated BW 755C, a potent
inhibitor of both lipoxygenase and cyclooxygenase, in eight intact
anesthetized dogs with acute left lower lobe atelectasis. We examined two
manifestations of hypoxic vasoconstriction: shunt fraction, as an inverse
indicator of regional constriction in response to local hypoxia, and the
pulmonary pressor response to global alveolar hypoxia, as an index of
general hypoxic vasoconstriction. During normoxia, shunt fraction, measured
using a sulfur hexafluoride infusion, was 32.0 +/- 7.0%. The pulmonary
pressor response to hypoxia, defined as the increase in pulmonary
end-diastolic gradient produced by 10% O2 inhalation, averaged 4.5 +/- 1.8
mmHg. Then, during normoxia, BW 755C was administered. Shunt fraction fell
in all eight dogs from the previous mean of 32% to 25.5 +/- 6.1% (t = 6.5,
P less than 0.0005). The hypoxic pressor response rose in all dogs, from
the previous 4.5 mmHg to 9.0 +/- 3.5 mmHg (t = 4.5, P less than 0.005). BW
755C enhances hypoxic vasoconstriction, an effect consistent with its
activity as a cyclooxygenase inhibitor. These data do not support a
substantive role for the lipoxygenase pathway in hypoxic vasoconstriction.
