Prostaglandin I₂ mediates contraction and relaxation of vascular smooth muscle

Prostaglandin (PG) I₂ elicits a biphasic concentration-response curve in rat aorta: lower concentrations elicit relaxation, whereas at higher concentrations, the relaxation is reversed. The purpose of this study was to investigate 1) the nature of the receptors that mediate these effects and 2) whether the relaxant efficacy of PGI₂ is decreased at higher PGI₂ concentrations by PGI₂-induced contraction. PGI₂ (1 μM), the stable PGI₂ analogue carbacyclin (1 μM), and PGE₁ (3 μM) induced maximal relaxations of 55, 40, and 63%, respectively, of norepinephrine-contracted aorta, whereas higher concentrations of PGI₂, carbacyclin, and PGE₁ reversed the relaxation. The thromboxane (Tx) A₂-PGH₂ receptor antagonist, SQ-29548, abolished the reversal of the PGI₂-, carbacyclin-, and PGE₁-induced relaxation, and maximal relaxations to PGI₂, carbacyclin, and PGE₁ increased to 73, 85, and 89% of the norepinephrine contraction, respectively, with 50% effective concentrations of 0.16, 0.43, and 0.83 μM, respectively. PGE₂ and PGD₂ did not induce relaxation in the presence or absence of SQ- 29548. PGI₂ and carbacyclin displaced the TxA₂-PGH₂ receptor ligand 1S- [1α,2β(5Z),3α(1E,3S),4α]-7-{3-[3-hydroxy-4-(p-[¹²⁵I]iodophenoxy)-1- butenyl]7-oxabicyclo[2.2.1]hept-2-yl}-5-heptenoic acid from cultured rat aorta smooth muscle cells with concentrations of competing ligand that displaced 50% of the specifically bound radioligand from its binding site of 6.0 and 2.3 μM, respectively. These results suggest that 1) PGI₂ induces relaxation through a PGI₂-PGE₁ receptor, and 2) higher concentrations of PGI₂ act at the TxA₂-PGH₂ receptor to decrease PGI₂-induced relaxation.