AJP - Lung Cellular and Molecular Physiology, Vol 267, Issue 5 602-L608, Copyright © 1994 by American Physiological Society
Prostaglandin B2-induced pulmonary hypertension is mediated by TxA2/PGH2 receptor stimulation
F. Liu, J. A. Orr and J. Y. Wu
Department of Physiology and Cell Biology, University of Kansas, Lawrence 66045.
We investigated whether the physiological effects of prostaglandin B2
(PGB2) in the pulmonary circulation might be due to stimulation of
thromboxane A2-prostaglandin H2 (TxA2/PGH2) receptors. In seven
anesthetized rabbits, intravenous infusion of PGB2 (5.0 micrograms/kg)
caused pulmonary hypertension as evidenced by increases in right
ventricular systolic blood pressure. The magnitude of the pulmonary
hypertension was comparable to that observed after infusion of the TxA2
mimetic U-46619 at a significantly lower dose (0.5 micrograms/kg),
indicating that the effects of PGB2 in the intact animal are similar to
TxA2 but less potent. Additionally, the TxA2/PGH2-receptor antagonist
SQ-29548 blocked the pulmonary blood pressure responses elicited by PGB2.
Receptor-binding studies using the TxA2 receptor ligand [3H]SQ-29548
indicated that PGB2 was a potent competitor for TxA2/PGH2 receptor binding.
In agreement with the results from the intact animal, however, the efficacy
of inhibition with PGB2 was significantly less than that measured for the
TxA2 agonist U-46619. All of these results are consistent with the
hypothesis that the physiological effects of PGB2 are mediated by
stimulation of TxA2/PGH2 receptors.
