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 microM) 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 (0.1-0.5 microM) 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.
Zhao
Y J
YJ
Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Wang
J
J
Tod
M L
ML
Rubin
L J
LJ
Yuan
X J
XJ
D000818:Animals; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000494:pharmacology*; D008297:Male; D011652:Pulmonary Circulation / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017482:Receptors, Thromboxane / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects*
D017482:Receptors, Thromboxane; D011464:Epoprostenol