Prostaglandin E2 modulation of blood pressure homeostasis: Studies in rodent models

Hypertension is a well established risk factor for cardiovascular diseases such as stroke and is the leading cause of chronic kidney failure. Although a number of pharmacologic agents are available for the treatment of hypertension including agents that affect the renin–angiotensin–aldosterone system (RAAS), unmet needs in the treatment of hypertension suggest that identification of novel pharmacological targets would be an important healthcare goal. One potential target is prostaglandin E2 (PGE2), a potent lipid mediator with a diverse and sometimes opposing range of biological effects. PGE2 signals through four subtypes of G-protein coupled receptors designated EP1 through EP4. PGE2 functions primarily as a vasodepressor; under certain conditions PGE2 administration mediates vasopressor activity. This review focuses on the current understanding of the roles of PGE2 receptors in vascular reactivity, hypertension and end-organ damage.

► PGE2 receptors are key modulators of blood pressure control, where EP receptors have functionally antagonistic actions.
► Activation of EP2 and EP4 receptors generally lowers blood pressure.
► Activation of EP1 and EP3 receptors generally raises blood pressure.
► Systemic infusion of PGE2 leads to a fall in mean arterial pressure by activation of the EP2 receptor.
► Intracerebroventricular infusion of PGE2 leads to a rise in mean arterial pressure by activation of the EP3 receptor.