PROSTAGLANDIN B-2-INDUCED PULMONARY-HYPERTENSION IS MEDIATED BY TXA(2) PGH(2) RECEPTOR STIMULATION/

We investigated whether the physiological effects of prostaglandin B-2 (PGB(2)) in the pulmonary circulation might be due to stimulation of thromboxane A(2)-prostaglandin H-2 (TxA(2)/PGH(2)) receptors. In seven anesthetized rabbits, intravenous infusion of PGB(2) (5.0 mu g/kg) ca used pulmonary hypertension as evidenced by increases in right ventric ular systolic blood pressure. The magnitude of the pulmonary hypertens ion was comparable to that observed after infusion of the TxA(2) mimet ic U-46619 at a significantly lower dose (0.5 mu g/kg), indicating tha t the effects of PGB(2) in the intact animal are similar to TxA(2) but less potent. Additionally, the TxA(2)/PGH(2)-receptor antagonist SQ-2 9548 blocked the pulmonary blood pressure responses elicited by PGB(2) . Receptor-binding studies using the TxA(2) receptor ligand [H-3]SQ-29 548 indicated that PGB(2) was a potent competitor for TxA(2)/PGH(2) re ceptor binding. In agreement with the results from the intact animal, however, the efficacy of inhibition with PGB(2) was significantly less than that measured for the TxA(2) agonist U-46619. All of these resul ts are consistent with the hypothesis that the physiological effects o f PGB(2) are mediated by stimulation of TxA(2)/PGH(2) receptors.