title: Direct vasoconstrictor effect of prostaglandin E2 on renal interlobular arteries: role of the EP3 receptor.
abstract: Evidence indicates that prostaglandin E(2) (PGE(2)) preferentially affects preglomerular renal vessels. However, whether this is limited to small-caliber arterioles or whether larger vessels farther upstream also respond to PGE(2) is currently unclear. In the present study, we first investigated the effects of PGE(2) 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 PGE(2), both under basal conditions and after the induction of vascular tone. By contrast, smaller vessels, i.e., distal ILAs and afferent arterioles, exhibited PGE(2)-induced vasodilation. Endothelium removal and pretreatment of single, isolated proximal ILAs with an EP1 receptor blocker (SC51322, 1 micromol/l) or a thromboxane A(2) receptor blocker (SQ29548, 1 micromol/l) did not prevent vasoconstriction to PGE(2). Furthermore, in the presence of SC51322, responses of these vessels to PGE(2) and the EP1/EP3 agonist sulprostone were superimposable, indicating that PGE(2)-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 PGE(2) to normal isolated kidneys induced a biphasic flow response, i.e., an initial flow increase at PGE(2) concentrations <or=0.1 micromol/l followed by a flow decrease at 1 mumol/l PGE(2). Thus our results demonstrate that PGE(2) affects multiple segments of the preglomerular vascular tree in a different way. At the level of the proximal ILAs, PGE(2) had a direct vasoconstrictor action mediated by EP3 receptors.
authors.affiliation: Laboratory for Physiology, Institute for Cardiovascular Research, VU University Medical Center, van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
authors.forename: William F
authors.initials: WF
authors.lastname: van Rodijnen
authors.forename: Iolente J
authors.initials: IJ
authors.lastname: Korstjens
authors.forename: Natalee
authors.initials: N
authors.lastname: Legerstee
authors.forename: Piet M
authors.initials: PM
authors.lastname: Ter Wee
authors.forename: Geert-Jan
authors.initials: GJ
authors.lastname: Tangelder
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D006869:Hydronephrosis / Q000503:physiopathology; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000098:blood supply*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D009638:Norepinephrine / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D018078:Receptors, Prostaglandin E / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058308:Receptors, Prostaglandin E, EP3 Subtype; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000037:antagonists & inhibitors; D012079:Renal Circulation / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; C545637:Ptger1 protein, rat; C545649:Ptger3 protein, rat; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058308:Receptors, Prostaglandin E, EP3 Subtype; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C016767:sulprostone; C045749:SQ 29548; D015232:Dinoprostone; D009638:Norepinephrine