Role of EP2
receptors in control of murine renal hemodynamics
The kidney plays a central role in longterm regulation of arterial blood pressure and salt and water homeostasis. This is achieved in part by the local actions of paracrine and autacoid mediators such as the arachidonic acid-prostanoid system. The present study tested the role of specific PGE2 E-prostanoid (EP) receptors in the regulation of renal hemodynamics and vascular reactivity to PGE2. Specifically, we determined the extent to which the EP2 and EP3 receptor subtypes mediate the actions of PGE2 on renal vascular tone. Renal blood flow (RBF) was measured by ultrasonic flowmetry, whereas 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 controls (+/+). Our results do not support a unique role of the EP2 receptor in regulating overall renal hemodynamics. Baseline renal hemodynamics in EP2-/- 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 not differ statistically from control mice (RBF +/+: 4.0 ± 0.5 ml·min 1·100 g kidney wt -1; RVR +/+: 25.4 ± 4.9 mmHg·ml 1·min·100 g kidney wt-1). This was also the case for the peak RBF increase after local PGE2 (500 ng) injection into the renal artery (EP2-/-: 116 ± 4 vs. +/+: 112 ± 2% baseline RBF). In contrast, we found that the absence of EP3 receptors in EP3-/- 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 decrease (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 PGE2 into the renal artery caused more pronounced renal vasodilation in EP3-/- mice (128 ± 2% of basal RBF, P < 0.05 vs. +/+). We conclude that EP3 receptors mediate vasoconstriction in the kidney of male mice and its actions are tonically active in the basal state. Furthermore, EP3 receptors are capable of buffering PGE2-mediated renal vasodilation.
Audoly, LP; Ruan, X; Wagner, VA; Goulet, JL; Tilley, SL; Koller, BH; Coffman, TM; Arendshorst, WJ
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