Pulmonary vasoconstrictor effects of prostacyclin in rats: Potential role of thromboxane receptors

Endogenous prostacyclin (PGI₂; epoprostenol) is a potent endothelium- derived pulmonary vasodilator. However, the effects of exogenous PGI₂ on isolated arteries could be either relaxant or contractile, depending on the species and organ studied. The present study investigated the distal pathways involved in the PGI₂-induced contraction in rat intrapulmonary artery (PA) and relaxation in lamb PA. When vessels were precontracted with 30 mM K⁺, PGI₂ (1 μM) induced relaxation in lamb PA but caused contraction in rat PA. Use of 30 mM K⁺, phenylephrine, serotonin, angiotensin II, or hypoxia to precontract the vessels did not alter the contractile effect of PGI₂ in rat PA. Nevertheless, PGI₂ produced a mild relaxation in rat PA precontracted by U-46619, a thromboxane A₂ (TxA₂)- receptor agonist, whereas the TxA₂-receptor blocker SQ-29548 (0.10.5 μM) abolished the contractile response in rat PA. These data suggest that PGI₂- induced contraction is mediated by activation of TxA₂ receptors. The PGI₂- induced modest relaxation in rat PA, which was only observed when TxA₂ receptors were blocked by SQ-29548, suggests that the PGI₂-mediated vasorelaxant pathway is diminished in these vessels. Simultaneous application of forskolin, an adenylate cyclase activator, and rolipram, a phosphodiesterase inhibitor, caused similar relaxation in both rat and lamb PA. This suggests that the adenosine 3',5'-cyclic monophosphate-dependent relaxing pathway is intact in rat PA and is comparable to that in lamb PA. On the basis of these data, we conclude that the pathways responsible for the paradoxical effects of PGI₂ on rat and lamb PA are located upstream of the adenosine 3',5'-cyclic monophosphate-dependent relaxing pathway and that a paucity of PGI₂ receptors in rat PA may be responsible.