title: Contribution of prostaglandin EP(2) receptors to renal microvascular reactivity in mice.
abstract: The present studies were performed to determine the contribution of EP(2) receptors to renal hemodynamics by examining afferent arteriolar responses to PGE(2), butaprost, sulprostone, and endothelin-1 in EP(2) receptor-deficient male mice (EP(2)-/-). Afferent arteriolar diameters averaged 17.8 +/- 0.8 microm in wild-type (EP(2)+/+) mice and 16.7 +/- 0.7 microm in EP(2)-/- mice at a renal perfusion pressure of 100 mmHg. Vessels from both groups of mice responded to norepinephrine (0.5 microM) with similar 17-19% decreases in diameter. Diameters of norepinephrine-preconstricted afferent arterioles increased by 7 +/- 2 and 20 +/- 6% in EP(2)+/+ mice in response to 1 microM PGE(2) and 1 microM butaprost, respectively. In contrast, afferent arteriolar diameter of EP(2)-/- mice decreased by 13 +/- 3 and 16 +/- 6% in response to PGE(2) and butaprost. The afferent arteriolar vasoconstriction to butaprost in EP(2)-/- mice was eliminated by angiotensin-converting enzyme inhibition. Sulprostone, an EP(1) and EP(3) receptor ligand, decreased afferent arteriolar diameter in both groups; however, the vasoconstriction in the EP(2)-/- mice was greater than in the EP(2)+/+ mice. Endothelin-1-mediated afferent arteriolar diameter responses were enhanced in EP(2)-/- mice. Afferent arteriolar diameter decreased by 29 +/- 7% in EP(2)-/- and 12 +/- 7% in EP(2)+/+ mice after administration of 1 nM endothelin-1. These results demonstrate that the EP(2) receptor mediates a portion of the PGE(2) afferent arteriolar vasodilation and buffers the renal vasoconstrictor responses elicited by EP(1) and EP(3) receptor activation as well as endothelin-1.
authors.affiliation: Vascular Biology Center, Department of Physiology, Medical College of Georgia, Augusta, Georgia 30912, USA. jdimig@mail.mcg.edu
authors.forename: John D
authors.initials: JD
authors.lastname: Imig
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Breyer
authors.forename: Richard M
authors.initials: RM
authors.lastname: Breyer
mesh_terms: D000527:Alprostadil / Q000031:analogs & derivatives* / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000031:analogs & derivatives* / Q000494:pharmacology; D019332:Endothelin-1 / Q000008:administration & dosage / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009638:Norepinephrine / Q000494:pharmacology; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology; D018078:Receptors, Prostaglandin E / Q000502:physiology*; D058307:Receptors, Prostaglandin E, EP2 Subtype; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D016861:Cyclooxygenase Inhibitors; D019332:Endothelin-1; D011459:Prostaglandins E, Synthetic; C545645:Ptger2 protein, mouse; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; C016767:sulprostone; D000527:Alprostadil; C048491:butaprost; D015232:Dinoprostone; D009638:Norepinephrine