title: Endothelium modulates vasoconstrictor response to prostaglandin I2 in rat mesenteric resistance arteries: interaction between EP1 and TP receptors.
abstract: OBJECTIVE
  Prostacyclin (PGI(2)) is usually described as an endothelium-derived vasodilator, but it can also induce vasoconstriction. We studied the vasomotor responses to PGI(2) in resistance arteries and the role of thromboxane (TP) and prostaglandin E(2) (EP) receptors in this effect.
  
  
  METHODS
  Mesenteric resistance arteries were obtained from Sprague-Dawley rats. Vasomotion to PGI(2) was studied in segments of these arteries with and without endothelium and in presence of the nitric oxide (NO) synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME), the potassium channel blockers apamin plus charybdotoxin, the non-selective EP receptor antagonist AH6809, the selective TP receptor antagonist SQ29548 or the EP(1) receptor antagonist SC19220. PGI(2)-induced NO release was analysed in the absence or presence of SQ29548, AH6809 or SC19220.
  
  
  RESULTS
  PGI(2) caused contractions in arterial segments that were increased by endothelium removal, L-NAME or L-NAME plus apamin plus charybdotoxin and abolished by SQ29548. In segments with endothelium, AH6809 or SC19220 almost abolished the contractions to PGI(2); this effect was prevented by L-NAME, L-NAME plus apamin plus charybdotoxin or by endothelium removal. PGI(2) induced NO release that was inhibited by the prostacyclin receptor (IP receptor) antagonist, RO1138452, and increased by SQ29548, SC19220 and AH6809. The increase in NO release induced by these separate drugs was inhibited by RO1138452.
  
  
  CONCLUSIONS
  PGI(2) activated the TP receptor in mesenteric resistance arteries and produced vasoconstriction, which the endothelium modulated through TP and EP(1) receptors. PGI(2) also released endothelium-derived hyperpolarizing factor and, through IP receptor activation, induced NO release, which in turn, was antagonized by TP and EP(1) receptor activation.
authors.affiliation: Departamento de Fisiologia e Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Pernambuco, Recife, Brazil.
authors.forename: F E
authors.initials: FE
authors.lastname: Xavier
authors.forename: J
authors.initials: J
authors.lastname: Blanco-Rivero
authors.forename: M
authors.initials: M
authors.lastname: Ferrer
authors.forename: G
authors.initials: G
authors.lastname: Balfagón
mesh_terms: D000818:Animals; D001685:Biological Factors / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D011464:Epoprostenol / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018078:Receptors, Prostaglandin E / Q000187:drug effects / Q000378:metabolism*; D058306:Receptors, Prostaglandin E, EP1 Subtype; D017482:Receptors, Thromboxane / Q000187:drug effects / Q000378:metabolism*; D014661:Vasoconstriction / Q000502:physiology
chemical_list: D001685:Biological Factors; C545637:Ptger1 protein, rat; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D017482:Receptors, Thromboxane; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide; D011464:Epoprostenol; D019331:NG-Nitroarginine Methyl Ester