J Role of COX-2-derived PGE(2) on vascular stiffness and function in hypertension
Por:
Avendano, MS, Martinez-Revelles, S, Aguado, A, Simoes, MR, Gonzalez-Amor, M, Palacios, R, Guillem-Llobat, P, Vassallo, DV, Vila, L, Garcia-Puig, J, Beltran, LM, Alonso, MJ, Cachofeiro, MV, Salaices, M, Briones, AM
Publicada:
1 may 2016
Resumen:
Background and PurposeProstanoids 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.
Experimental ApproachSpontaneously hypertensive rats (SHR) and angiotensin II (AngII)-infused (1.44 mgkg(-1)day(-1), 2 weeks) mice were treated with the COX-2 inhibitor celecoxib (25 mgkg(-1)day(-1) i.p) or with the EP1 receptor antagonist SC19220 (10 mgkg(-1)day(-1) i.p.). COX-2(-/-) mice with or without AngII infusion were also used.
Key ResultsCelecoxib 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 PGE(2) production in vascular tissue, normalized by celecoxib. Celecoxib treatment also decreased AngII-induced macrophage infiltration and TNF- 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 and ImplicationsCOX-2 and EP1 receptors participate in the increased extracellular matrix deposition and vascular stiffness, the impaired vascular function and inflammation in hypertension. Targeting PGE(2) receptors might have benefits in hypertension-associated vascular damage.
Filiaciones:
Avendano, MS:
Univ Autonoma Madrid, Dept Farmacol, Hosp Univ La Paz IdiPAZ, Inst Invest, E-28049 Madrid, Spain
Martinez-Revelles, S:
Univ Autonoma Madrid, Dept Farmacol, Hosp Univ La Paz IdiPAZ, Inst Invest, E-28049 Madrid, Spain
Aguado, A:
Univ Autonoma Madrid, Dept Farmacol, Hosp Univ La Paz IdiPAZ, Inst Invest, E-28049 Madrid, Spain
Simoes, MR:
Univ Autonoma Madrid, Dept Farmacol, Hosp Univ La Paz IdiPAZ, Inst Invest, E-28049 Madrid, Spain
Univ Fed Espirito Santo, Dept Physiol Sci, Vitoria, Brazil
Gonzalez-Amor, M:
Univ Autonoma Madrid, Dept Farmacol, Hosp Univ La Paz IdiPAZ, Inst Invest, E-28049 Madrid, Spain
Palacios, R:
Univ Autonoma Madrid, Dept Farmacol, Hosp Univ La Paz IdiPAZ, Inst Invest, E-28049 Madrid, Spain
Guillem-Llobat, P:
UAM CSIC, Ctr Biol Mol Severo Ochoa, Madrid, Spain
Vassallo, DV:
Univ Fed Espirito Santo, Dept Physiol Sci, Vitoria, Brazil
Vila, L:
Inst Invest Biomed IIB St Pau, Lab Angiol Biol Vasc & Inflamac, Barcelona, Spain
Garcia-Puig, J:
UAM, IdiPaz, Hosp Univ La Paz, Med Interna Serv, Madrid, Spain
Beltran, LM:
UAM, IdiPaz, Hosp Univ La Paz, Med Interna Serv, Madrid, Spain
Alonso, MJ:
Univ Rey Juan Carlos, Dept Ciencias Basicas Salud, Alcorcon, Spain
Cachofeiro, MV:
Univ Complutense, Fac Med, Dept Fisiol, E-28040 Madrid, Spain
Salaices, M:
Univ Autonoma Madrid, Dept Farmacol, Hosp Univ La Paz IdiPAZ, Inst Invest, E-28049 Madrid, Spain
Briones, AM:
Univ Autonoma Madrid, Dept Farmacol, Hosp Univ La Paz IdiPAZ, Inst Invest, E-28049 Madrid, Spain
Bronze, Green Published
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