ObjectiveOur objective was to determine whether the selective angiotensin II type 1 (AT1) receptor antagonist losartan interacts with thromboxane A2/endoperoxide (TXA2/PGH2) receptors.Methods:We measured changes in mean pulmonary arterial pressure (MPAP) induced by the stable TXA2analogue U-46619 during blockade of either TXA2/PGH2or AT1receptors in anesthetized, open-chest rats (four to eight per group).Results:U-46619 (1.25 and 10 μg/kg) dose-dependently increased MPAP. The 1.25 μg/kg dose of U-46619 increased MPAP (±51%,P<0.01), was dose-dependently inhibited by the TXA2/PGH2receptor antagonist SQ 29,548 (±94 and 102% at 0.63 and 2.5 mg/kg, respectively; bothP<0.05). Losartan also dose-dependently reduced this increase (±11 and 65% at 2.5 and 10 mg/kg, respectively;P=NS andP<0.05, respectively). Furthermore, losartan dose-dependently prevented the increase in MPAP (±112%) induced by an eightfold higher dose of U-46619 (10 μg/kg) by ±9 and 75% at doses of 10 and 40 mg/kg, respectively;P=NS andP<0.05, respectively.Conclusions:Thus, selective activation of TXA2/PGH2receptors by the TXA2analogue U-46610 induced pulmonary hypertension, which was specifically inhibited by the TXA2/PGH2receptor antagonist SQ 29,548 and the AT1receptor antagonist losartan, suggesting that the latter exerts antagonist activity at TXA2/PGH2receptors.