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Am J Physiol Renal Physiol 292: F1094-F1101, 2007. First published December 5, 2006; doi:10.1152/ajprenal.00351.2005
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Direct vasoconstrictor effect of prostaglandin E2 on renal interlobular arteries: role of the EP3 receptor

William F. van Rodijnen,1 Iolente J. Korstjens,1 Natalee Legerstee,1 Piet M. ter Wee,2 and Geert-Jan Tangelder1

1Laboratory for Physiology and 2Department of Nephrology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands

Submitted 26 August 2005 ; accepted in final form 27 November 2006

Evidence indicates that prostaglandin E2 (PGE2) preferentially affects preglomerular renal vessels. However, whether this is limited to small-caliber arterioles or whether larger vessels farther upstream also respond to PGE2 is currently unclear. In the present study, we first investigated the effects of PGE2 along the preglomerular vascular tree and subsequently focused on proximal interlobular arteries (ILAs). Proximal ILAs in hydronephrotic rat kidneys as well as isolated vessels from normal kidneys constricted in response to PGE2, both under basal conditions and after the induction of vascular tone. By contrast, smaller vessels, i.e., distal ILAs and afferent arterioles, exhibited PGE2-induced vasodilation. Endothelium removal and pretreatment of single, isolated proximal ILAs with an EP1 receptor blocker (SC51322, 1 µmol/l) or a thromboxane A2 receptor blocker (SQ29548, 1 µmol/l) did not prevent vasoconstriction to PGE2. Furthermore, in the presence of SC51322, responses of these vessels to PGE2 and the EP1/EP3 agonist sulprostone were superimposable, indicating that PGE2-induced vasoconstriction is mediated by EP3 receptors on smooth muscle cells. Immunohistochemical staining of proximal ILAs confirmed the presence of EP3 receptor protein on these cells and the endothelium. Adding PGE2 to normal isolated kidneys induced a biphasic flow response, i.e., an initial flow increase at PGE2 concentrations ≤0.1 µmol/l followed by a flow decrease at 1 µmol/l PGE2. Thus our results demonstrate that PGE2 affects multiple segments of the preglomerular vascular tree in a different way. At the level of the proximal ILAs, PGE2 had a direct vasoconstrictor action mediated by EP3 receptors.

interlobular arteries; vasoconstriction



Address for reprint requests and other correspondence: G.-J. Tangelder, Laboratory for Physiology, Institute for Cardiovascular Research, VU Univ. Medical Center, van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands (e-mail: geertjan.tangelder{at}vumc.nl)




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