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 microM), the stable PGI2 analogue carbacyclin (1 microM), and PGE1 (3 microM) 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 microM, 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-[1 alpha,2 beta(5Z),3 alpha(1E,3S),4 alpha]-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 microM, 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.