Roles of EP Receptors in the Regulation of Fluid Balance and Blood Pressure

Abstract

Prostaglandin E2 (PGE2) is an important prostanoid expressing throughout the kidney and cardiovascular system. Despite the diverse effects on fluid metabolism and blood pressure, PGE2 is implicated in sustaining volume and hemodynamics homeostasis. PGE2 works through four distinct E-prostanoid (EP) receptors which are G protein-coupled receptors. To date, pharmacological specific antagonists and agonists of all four subtypes of EP receptors and genetic targeting knockout mice for each subtype have helped in uncoupling the diverse functions of PGE2 and discriminating the respective characteristics of each receptor. In this review, we summarized the functions of individual EP receptor subtypes in the renal and blood vessels and the molecular mechanism of PGE2-induced fluid metabolism and blood pressure homeostasis.

The Link between Prostanoids and Cardiovascular Diseases

“…When it interacts with EP1 and EP3, it induces vasoconstriction, while it promotes vasodilatation when binding to EP2 and EP4 receptors. It is also involved in angiotensin-II-induced vasoconstriction [ 147 , 174 ].…”

Vasodilation and Blood Pressure-Lowering Effect of 3-Demethyl-2-Geranyl-4-Prenylbellidifoline, a Xanthone Obtained from Garcinia achachairu, in Hypertensive Rats

“…Among these, cyclooxygenase-derived prostanoids significantly influence vascular physiology. The balance and dynamic interplay of prostanoids in blood vessels contribute to regulating the vascular tone, controlling blood pressure, blood flow, and cardiovascular homeostasis [ 32 ]. Importantly, the incubation of indomethacin, a well-stablished cyclooxygenase inhibitor, was unable to modify DGP-mediated relaxation in Phe-contracted aortic rings, suggesting that these endothelial-derived prostanoids do not contribute to the vascular effects of this xanthone.…”

Studies in Zebrafish and Rat Models Support Dual Blockade of EP2 and EP4 (Prostaglandin E 2 Receptors Type 2 and 4) for Renoprotection in Glomerular Hyperfiltration and Albuminuria

“…25 However, it should be not dismissed that COX-derived prostaglandins including PGE 2 play an important role in maintaining renal homeostasis and may serve as physiological buffers, protecting kidney function under certain pathophysiological conditions, particularly in states associated with decreased effective arterial blood volume. 7,26,27 Given the multifaceted role of PGE 2 in the kidney, 7 we, therefore, first tested whether PGE 2 can in fact induce albuminuria in vivo in nondiabetic models. The latter was indeed confirmed in zebrafish experiments.…”