The prostacyclin (IP) receptor agonists, treprostinil, iloprost and the 
selexipag metabolite, MRE-269 (ACT-333679) were evaluated in rat distal 
pulmonary blood vessels. Small pulmonary arteries and veins were pre-contracted 
with the thromboxane mimetic, U46619 (25 and 100nM, respectively), and 
relaxation determined with and without IP receptor antagonists, RO1138452 and 
RO3244794. In arteries, treprostinil was a more potent vasorelaxant than 
iloprost, while the efficacy of iloprost was greater. In pulmonary arteries, 
treprostinil-induced relaxation was essentially abolished by both IP antagonists 
(1μM), while responses to iloprost were partially inhibited. Both treprostinil 
and iloprost were equipotent, prominently relaxing pulmonary veins with 
responses being similarly and partially sensitive to IP antagonists. In 
contrast, RO1138452 failed to inhibit relaxations to MRE-269 in either pulmonary 
arteries or veins, suggesting no involvement of typical IP receptors. Thus, rat 
pulmonary tissues cannot be considered appropriate to assess classical IP 
receptors using the proposed highly selective non-prostanoid agonist MRE-269, 
contrasting with the IP receptor agonism profile of prostacyclin analogues, 
iloprost and treprostinil.