PROSTAGLANDIN I-2 MEDIATES CONTRACTION AND RELAXATION OF VASCULAR SMOOTH-MUSCLE

Prostaglandin (PG) 12 elicits a biphasic concentration-response curve in rat aorta: lower concentrations elicit relaxation, whereas at highe r concentrations, the relaxation is reversed. The purpose of this stud y was to investigate 1) the nature of the receptors that mediate these effects and 2) whether the relaxant efficacy of PGI(2) is decreased a t higher PGI(2) concentrations by PGI(2)-induced contraction. PGI(2) ( 1 mu M), the stable PGI(2) analogue carbacyclin (1 mu M), and PGE(1) ( 3 mu M) induced maximal relaxations of 55, 40, and 63%, respectively, of norepinephrine-contracted aorta, whereas higher concentrations of P GI(2), carbacyclin, and PGE(1) reversed the relaxation. The thromboxan e (Tx) A(2)-PGH(2) receptor antagonist, SQ-29548, abolished the revers al of the PGI(2)-, carbacyclin-, and PGE(1)-induced relaxation, and ma ximal relaxations to PGI(2), carbacyclin, and PGE(1) increased to 73, 85, and 89% of the norepinephrine contraction, respectively, with 50% effective concentrations of 0.16, 0.43, and 0.83 mu M, respectively. P GE(2) and PGD(2) did not induce relaxation in the presence or absence of SQ-29548. PGI(2) and carbacyclin displaced the TxA(2)-PGH(2) recept or ligand 1S-[1 alpha,2 beta(5Z),3 alpha(1E,3S),4 -butenyl]7-oxabicycl o[2.2.1]hept-2-yl}-5-heptenoic acid from cultured rat aorta smooth mus cle cells with concentrations of competing ligand that displaced 50% o f the specifically bound radioligand from its binding site of 6.0 and 2.3 mu M, respectively. These results suggest that 1) PGI(2) induces r elaxation through a PGI(2)-PGE(1) receptor, and 2) higher concentratio ns of PGI(2) act at the TxA(2)-PGH(2) receptor to decrease PGI(2)-indu ced relaxation.