Role of EP2 and EP3 PGE(2) receptors in control of murine renal hemodynamics

The kidney plays a central role in longterm regulation of arterial blood pr essure and salt and water homeostasis. This is achieved in part by the loca l actions of paracrine and autacoid mediators such as the arachidonic acid- prostanoid system. The present study tested the role of specific PGE(2) E-p rostanoid (EP) receptors in the regulation of renal hemodynamics and vascul ar reactivity to PGE(2). Specifically, we determined the extent to which th e EP2 and EP3 receptor subtypes mediate the actions of PGE(2) on renal vasc ular tone. Renal blood flow (RBF) was measured by ultrasonic flowmetry, whe reas vasoactive agents were injected directly into the renal artery of male mice. Studies were performed on two independent mouse lines lacking either EP2 or EP3 (-/-) receptors and the results were compared with wild-type co ntrols (+/+). Our results do not support a unique role of the EP2 receptor in regulating overall renal hemodynamics. Baseline renal hemodynamics in EP 2-/- mice [RBF EP2 -/-: 5.3 +/- 0.8 ml.min(-1) . 100 g kidney wt(-1); renal vascular resistance (RVR) 19.7 +/- 3.6 mmHg.ml(-1),min.g kidney wt] did no t differ statistically from control mice (RBF +/+: 4.0 +/- 0.5 ml.min(-1).1 00 g kidney wt(-1); RVR +/+: 25.4 +/- 4.9 mmHg.ml(-1).min(-1).100 g kidney wt(-1)). This was also the case for the peak RBF increase after local PGE(2 ) (500 ng) injection into the renal artery (EP2 -/-: 116 +/- 4 vs. +/+: 112 +/- 2% baseline RBF). In contrast, we found that the absence of EP3 recept ors in EP2 -/- mice caused a significant increase (43%) in basal RBF (7.9 /- 0.8 ml.min(-1).g kidney wt(-1), P< 0.05 vs. +/+) and a significant decre ase (41%) in resting RVR (11.6 +/- 1.4 mmHg.ml(-1).min.g kidney wt(-1), P< 0.05 vs. +/+). Local administration of 500 ng of PGE(2) into the renal arte ry caused more pronounced renal vasodilation in EP3 -/- mice (128 +/- 2% of basal RBF, P< 0.05 vs. +/+). We conclude that EP3 receptors mediate vasoco nstriction in the kidney of male mice and its actions are tonically active in the basal state. Furthermore, EP3 receptors are capable of buffering PGE (2) mediated renal vasodilation.