Microsomal prostaglandin E synthase-1 and blood pressure regulation.

Abstract

Prostaglandin E (PGE)(2) is a major arachidonic acid metabolite in a wide variety of tissues and is implicated in the control of inflammatory as well as physiological responses. At least three major forms of PGE synthase (PGES) have recently been cloned and characterized: membrane-associated PGES (mPGES)-1, mPGES-2, and cytosolic PGES (cPGES). Among them, mPGES-1 is highly inducible by cytokine and is critically involved in pain and inflammatory responses. Emerging evidence suggests that mPGES-1 may also participate in blood pressure (BP) regulation through an impact on renal and vascular functions. Within the kidney, mPGES-1 predominates in the distal nephron where its expression is highly inducible by salt loading. Mice lacking mPGES-1 exhibit blunted natriuretic response paralleled with remarkably suppressed nitric oxide production, leading to salt-sensitive hypertension. These mice also exhibit an exaggerated hypertensive response to angiotensin II infusion. Together, these results suggest that mPGES-1 may be an important physiological regulator of BP.