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Prostaglandin E2 (PGE2) participates in blood pressure (BP) regulation through diverse mechanisms involving different tissues and different receptor subtypes. In general, PGE2 functions as a natriuretic factor in the kidney, promoting sodium excretion via inhibition of sodium transport in the distal nephron. On the other hand, PGE2 is a vasoactive agent capable of modulating vascular tone. PGE2 is a product of prostaglandin E synthase (PGES) and its biologic action is mediated by four EP receptors EP1-4 which exhibit distinct vasoactive properties. The best characterized PGES is microsomal prostaglandin E synthase-1 (mPGES-1), a viable target for the next generation of analgesic drugs. The review will focus on recent advances in understanding the roles of mPGES-1 and EP receptors in BP regulation.