Prostaglandin (PG) I2causes vasoconstriction in isolated blood vessels and yet lowers blood pressure. This study was conducted to study the vascular effects of PGE2on isolated vascular tissues. PGE2(10–2000 ng/ml) caused a concentration-dependent contraction of quiescent rat aortic rings, and the contraction was greater in endothelium-denuded than in endothelium-intact rings. PGE2-induced contraction was also enhanced by prior treatment of quiescent endothelium-intact rat aortic rings with the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), or the nitric oxide inactivator oxyhemoglobin. PGE2also caused an additional contraction of norepinephrine (NE)-precontracted rat aortic rings, but the additional contraction was similar in endothelium-intact or de-endothelialized rings. Pretreatment of endothelium-intact NE precontracted rings with L-NAME, or oxyhemoglobin, or the endothelin A and B receptors antagonist PD-142,893, or the cyclooxygenase inhibitor indomethacin did not affect the PGE2-induced contraction. On the other hand, pretreatment of endothelium-intact and denuded rings with the thromboxane A2/endoperoxide receptor antagonist SQ29548 almost completely abolished the PGE2-induced contraction. These observations indicate that the contractile effects of PGE2on quiescent rat aortic rings are endothelium-affectable, dependent but independent of endothelial integrity or function in NE-precontracted rings. Lastly, PGE2appears to cause contraction of rat aortic rings via activation of thromboxane A2/endoperoxide receptors on vascular smooth muscle cells.