title: Role of COX-2-derived PGE2 on vascular stiffness and function in hypertension.
abstract: OBJECTIVE
  Prostanoids derived from COX-2 and EP receptors are involved in vascular remodelling in different cardiovascular pathologies. This study evaluates the contribution of COX-2 and EP1 receptors to vascular remodelling and function in hypertension.
  
  
  METHODS
  Spontaneously hypertensive rats (SHR) and angiotensin II (AngII)-infused (1.44 mg · kg(-1) · day(-1), 2 weeks) mice were treated with the COX-2 inhibitor celecoxib (25 mg · kg(-1) · day(-1) i.p) or with the EP1 receptor antagonist SC19220 (10 mg · kg(-1) · day(-1) i.p.). COX-2(-/-) mice with or without AngII infusion were also used.
  
  
  RESULTS
  Celecoxib and SC19220 treatment did not modify the altered lumen diameter and wall : lumen ratio in mesenteric resistance arteries from SHR-infused and/or AngII-infused animals. However, both treatments and COX-2 deficiency decreased the augmented vascular stiffness in vessels from hypertensive animals. This was accompanied by diminished vascular collagen deposition, normalization of altered elastin structure and decreased connective tissue growth factor and plasminogen activator inhibitor-1 gene expression. COX-2 deficiency and SC19220 treatment diminished the increased vasoconstrictor responses and endothelial dysfunction induced by AngII infusion. Hypertensive animals showed increased mPGES-1 expression and PGE2 production in vascular tissue, normalized by celecoxib. Celecoxib treatment also decreased AngII-induced macrophage infiltration and TNF-α expression. Macrophage conditioned media (MCM) increased COX-2 and collagen type I expression in vascular smooth muscle cells; the latter was reduced by celecoxib treatment.
  
  
  CONCLUSIONS
  COX-2 and EP1 receptors participate in the increased extracellular matrix deposition and vascular stiffness, the impaired vascular function and inflammation in hypertension. Targeting PGE2 receptors might have benefits in hypertension-associated vascular damage.
authors: Dept. Farmacología, Universidad Autónoma de Madrid (UAM), Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid, Spain.
authors: M S
authors: MS
authors: Avendaño
authors: Dept. Farmacología, Universidad Autónoma de Madrid (UAM), Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid, Spain.
authors: S
authors: S
authors: Martínez-Revelles
authors: Dept. Farmacología, Universidad Autónoma de Madrid (UAM), Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid, Spain.
authors: A
authors: A
authors: Aguado
authors: Dept. Farmacología, Universidad Autónoma de Madrid (UAM), Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid, Spain.|Dept. Physiological Sciences, Federal University of Espirito Santo, Vitoria, Brazil.
authors: M R
authors: MR
authors: Simões
authors: Dept. Farmacología, Universidad Autónoma de Madrid (UAM), Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid, Spain.
authors: M
authors: M
authors: González-Amor
authors: Dept. Farmacología, Universidad Autónoma de Madrid (UAM), Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid, Spain.
authors: R
authors: R
authors: Palacios
authors: Centro de Biología Molecular "Severo Ochoa", UAM-CSIC, Madrid, Spain.
authors: P
authors: P
authors: Guillem-Llobat
authors: Dept. Physiological Sciences, Federal University of Espirito Santo, Vitoria, Brazil.
authors: D V
authors: DV
authors: Vassallo
authors: Laboratorio de Angiología, Biología Vascular e Inflamación, Instituto de Investigación Biomédica (IIB Sant Pau), Barcelona, Spain.
authors: L
authors: L
authors: Vila
authors: Servicio de Medicina Interna, Hospital Universitario La Paz, UAM, IdiPaz, Madrid, Spain.
authors: J
authors: J
authors: García-Puig
authors: Servicio de Medicina Interna, Hospital Universitario La Paz, UAM, IdiPaz, Madrid, Spain.
authors: L M
authors: LM
authors: Beltrán
authors: Dept Ciencias Básicas de la Salud, Universidad Rey Juan Carlos, Alcorcón, Spain.
authors: M J
authors: MJ
authors: Alonso
authors: Dept. Fisiología, Facultad de Medicina, Universidad Complutense, Madrid, Spain.
authors: M V
authors: MV
authors: Cachofeiro
authors: Dept. Farmacología, Universidad Autónoma de Madrid (UAM), Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid, Spain.
authors: M
authors: M
authors: Salaices
authors: Dept. Farmacología, Universidad Autónoma de Madrid (UAM), Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid, Spain.
authors: A M
authors: AM
authors: Briones
mesh_terms: D000818:Animals; D000068579:Celecoxib / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000172:deficiency / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D012531:Dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-acetylhydrazide / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D051379:Mice; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D058306:Receptors, Prostaglandin E, EP1 Subtype / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013329:Structure-Activity Relationship; D059289:Vascular Stiffness / Q000187:drug effects*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D058306:Receptors, Prostaglandin E, EP1 Subtype; D012531:Dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-acetylhydrazide; D051546:Cyclooxygenase 2; D000068579:Celecoxib; D015232:Dinoprostone