Pulmonary vasoconstrictor effects of prostacyclin in rats:
potential role of thromboxane receptors.
Zhao, Yi-Ju, Jian Wang, Mary L. Tod, Lewis J. Rubin, and Xiao-Jian
Yuan.
Department of Medicine, Division of Pulmonary and Critical Care
Medicine, Departments of Physiology and Pediatrics, University of
Maryland School of Medicine, Baltimore, Maryland; Cardiovascular
Institute, Chinese Academy of Medical Sciences and Peking Union
Medical College, Beijing, China
APStracts 3:0370A, 1996.
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 [mu]M)
induced relaxation in lamb PA, but caused contraction in rat PA.
Using 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 U46619, a thromboxane A2 (TXA2) receptor agonist,
while the TXA2 receptor blocker, SQ29548 (0.1-0.5 [mu]M), 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 SQ29548, 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 on both rat and lamb PA. This suggests that the
cAMP-dependent relaxing pathway is intact in rat PA, and comparable
to that in lamb PA. Based on these data, we conclude that the
pathways responsible for the paradoxical effects of prostacyclin on
rat and lamb PA are located upstream of the cAMP-dependent relaxing
pathway and that a paucity of prostacyclin receptors in rat PA may be
responsible.
Received 6 February 1996; accepted in final form 10 July 1996.
APS Manuscript Number A138-6.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 21 August 1996